41 results on '"Ai-Min Bao"'
Search Results
2. Distinct proteomic profiles in prefrontal subareas of elderly major depressive disorder and bipolar disorder patients
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Yang-Jian Qi, Yun-Rong Lu, Li-Gen Shi, Jeroen A. A. Demmers, Karel Bezstarosti, Erikjan Rijkers, Rawien Balesar, Dick Swaab, and Ai-Min Bao
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract We investigated for the first time the proteomic profiles both in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) of major depressive disorder (MDD) and bipolar disorder (BD) patients. Cryostat sections of DLPFC and ACC of MDD and BD patients with their respective well-matched controls were used for study. Proteins were quantified by tandem mass tag and high-performance liquid chromatography-mass spectrometry system. Gene Ontology terms and functional cluster alteration were analyzed through bioinformatic analysis. Over 3000 proteins were accurately quantified, with more than 100 protein expressions identified as significantly changed in these two brain areas of MDD and BD patients as compared to their respective controls. These include OGDH, SDHA and COX5B in the DLPFC in MDD patients; PFN1, HSP90AA1 and PDCD6IP in the ACC of MDD patients; DBN1, DBNL and MYH9 in the DLPFC in BD patients. Impressively, depending on brain area and distinct diseases, the most notable change we found in the DLPFC of MDD was ‘suppressed energy metabolism’; in the ACC of MDD it was ‘suppressed tissue remodeling and suppressed immune response’; and in the DLPFC of BD it was differentiated ‘suppressed tissue remodeling and suppressed neuronal projection’. In summary, there are distinct proteomic changes in different brain areas of the same mood disorder, and in the same brain area between MDD and BD patients, which strengthens the distinct pathogeneses and thus treatment targets.
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- 2022
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3. Sex differences in hippocampal β-amyloid accumulation in the triple-transgenic mouse model of Alzheimer’s disease and the potential role of local estrogens
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Yu-Ting Hu, Xin-Lu Chen, Ya-Nan Zhang, Hugo McGurran, Jochem Stormmesand, Nicole Breeuwsma, Arja Sluiter, Juan Zhao, Dick Swaab, and Ai-Min Bao
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Alzheimer’s disease ,triple-transgenic AD mouse ,β-amyloid ,17β-estradiol ,sex differences ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionEpidemiological studies show that women have a higher prevalence of Alzheimer’s disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1M146V, APPSwe, and TauP301L show sex differences in β-amyloid (Aβ) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17β-estradiol (E2) may regulate the expression of EGR1 and AChE.MethodsWe first sacrificed male and female 3xTg-AD mice at 3–4, 7–8, and 11–12 months and measured the levels of Aβ, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Aβ and intracellular EGR1 and AChE.ResultsFemale 3xTg-AD mice had higher levels of Aβ compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Aβ and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Aβ(1–42) was significantly decreased while intracellular EGR1 and AChE expression were elevated.DiscussionThis data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Aβ. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Aβ(1–42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels.
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- 2023
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4. Different oxytocin and corticotropin-releasing hormone system changes in bipolar disorder and major depressive disorder patients
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Lei Guo, Yang-Jian Qi, Hong Tan, Dan Dai, Rawien Balesar, Arja Sluiter, Joop van Heerikhuize, Shao-Hua Hu, Dick F. Swaab, and Ai-Min Bao
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Oxytocin ,Corticotropin-releasing hormone ,Bipolar disorder ,Major depressive disorder ,Hypothalamus ,Prefrontal cortex ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice. Methods: Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls. Findings: Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way. Interpretation: Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD. Funding: National Natural Science Foundation of China (81971268, 82101592).
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- 2022
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5. The human hypothalamus in mood disorders: The HPA axis in the center
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Ai-Min Bao and Dick F. Swaab
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
There are no specific structural neuropathological hallmarks found in the brain of mood disorders. Instead, there are molecular, functional and structural alterations reported in many brain areas. The neurodevelopmental underpinning indicated the presence of various genetic and developmental risk factors. The effect of genetic polymorphisms and developmental sequalae, some of which may start in the womb, result in functional changes in a network mediated by neurotransmitters and neuropeptides, which make the emotion- and stress-related brain systems more vulnerable to stressful events. This network of stress-related neurocircuits consists of, for instance, brainstem nuclei, the amygdala, habenula, prefrontal cortex and hypothalamus. Various nuclei of the hypothalamus form indeed one of the crucial hubs in this network. This structure concerns not only the hypothalamo-pituitary-adrenal (HPA) axis that integrate the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of depression, such as disordered day-night rhythm, lack of reward feelings, disturbed eating, sex, and disturbed cognitive functions. The present review will focus on the changes in the human hypothalamus in depression, with the HPA axis in the center. We will discuss the inordinate network of neurotransmitters and neuropeptides involved, with the hope to find the most vulnerable neurobiological systems and the possible development of tailor-made treatments for mood disorders in the future. Keywords: The hypothalamo-pituitary-adrenal axis, Glutamate, GABA, Neuropeptide, Sex differences
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- 2019
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6. Sexually Dimorphic Changes of Hypocretin (Orexin) in Depression
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Jing Lu, Juan Zhao, Rawien Balesar, Rolf Fronczek, Qiong-Bin Zhu, Xue-Yan Wu, Shao-Hua Hu, Ai-Min Bao, and Dick F. Swaab
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Depression ,Hypocretin ,Hypocretin receptors ,Hypothalamus ,Sex difference ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects. Methods: We quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat. Results: i) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats. Conclusions: The clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.
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- 2017
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7. Correction: ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines
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Shu-Xia Cao, Ying Zhang, Xing-Yue Hu, Bin Hong, Peng Sun, Hai-Yang He, Hong-Yan Geng, Ai-Min Bao, Shu-Min Duan, Jian-Ming Yang, Tian-Ming Gao, Hong Lian, and Xiao-Ming Li
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Medicine ,Science ,Biology (General) ,QH301-705.5 - Published
- 2019
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8. ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines
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Shu-Xia Cao, Ying Zhang, Xing-Yue Hu, Bin Hong, Peng Sun, Hai-Yang He, Hong-Yan Geng, Ai-Min Bao, Shu-Min Duan, Jian-Ming Yang, Tian-Ming Gao, Hong Lian, and Xiao-Ming Li
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ErbB4 ,noradrenergic neuron ,Locus coeruleus ,mania ,bipolar disorder ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, Erbb4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder.
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- 2018
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9. The stress systems in depression: a postmortem study
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Ai-Min Bao and Dick F. Swaab
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molecular mechanisms ,brain ,neurotransmitters ,neuromodulators ,genetics ,HPA axis ,sex steroids ,oxytocin ,orexin ,Psychiatry ,RC435-571 - Abstract
After trauma, depressive disorders are among the most frequent emerging diagnoses. However, although the symptoms of depression are well characterized, the molecular mechanisms underlying this disorder are largely unknown. Factors involved in the heterogeneous pathogenesis of depression include polymorphisms in stress-related genes, gender, age, developmental history, and environmental (traumatic) stressors such as epigenetic factors. These factors may make different parts of the stress-related brain systems more vulnerable to different stressful or traumatic life events or psychological stresses, causing alterations in a network of neurotransmitters and neuromodulators including amines, amino acids, nitric oxide (NO), and neuropeptides, and finally make individuals at risk for depression. The hypothalamo–pituitary–adrenal (HPA) axis has a prominent position in this network. With the postmortem brain material obtained from the Netherlands Brain Bank, we have carried on a series of studies with the aim to elucidate the specific changes in these systems in relation to special subtypes of depression. Our final destination is to set up tailor-made treatment for depressive patients on the basis of his/her developmental history, genetic and epigenetic background, and the vulnerability in particular neurobiological systems. This presentation is a review of our findings of changes in systems of sex steroids, receptors in the hypothalamic paraventricular nucleus, corticotrophin-releasing hormone, orexin, γ-aminobutyric acid, and NO in the etiology of depression, in relation to HPA activity, sex differences, and suicide.
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- 2014
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10. Sex differences in the neuropathological hallmarks of Alzheimer’s disease: focus on cognitively intact elderly individuals
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Hugo McGurran, Jackson Boonstra, Ai-Min Bao, Dick F. Swaab, Rawien Balesar, Arja A. Sluiter, Jochem Stormmesand, Yu-Ting Hu, Ronald W.H. Verwer, and Netherlands Institute for Neuroscience (NIN)
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Male ,0301 basic medicine ,Aging ,Histology ,Amyloid ,Physiology ,tau Proteins ,Disease ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,β amyloid ,Physiology (medical) ,mental disorders ,Entorhinal Cortex ,Humans ,Medicine ,Aged ,Aged, 80 and over ,Sex Characteristics ,Amyloid beta-Peptides ,business.industry ,Brain ,Neurofibrillary Tangles ,Entorhinal cortex ,030104 developmental biology ,Neurology ,Female ,Brain bank ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
AIMS Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, β-amyloid (Aβ) and hyperphosphorylated Tau (p-Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals. METHODS We first analysed the entire post-mortem brain collection of all non-demented 'controls' and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks. Second, we quantitatively studied possible sex differences in Aβ, Aβ42 and p-Tau in the entorhinal cortex of well-matched female (n = 31) and male (n = 21) clinically cognitively intact elderly individuals. RESULTS Women had significantly higher Braak stages for tangles and amyloid scores than men, after 80 years. In the cognitively intact elderly, women showed higher levels of p-Tau, but not Aβ or Aβ42, in the entorhinal cortex than men, and a significant interaction of sex with age was found only for p-Tau but not Aβ or Aβ42. CONCLUSIONS Enhanced p-Tau in the entorhinal cortex may play a major role in the vulnerability to AD in women.
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- 2021
11. Sex differences in hippocampal b-amyloid accumulation in the triple-transgenic mouse model of Alzheimer's disease and the potential role of local estrogens.
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Yu-Ting Hu, Xin-Lu Chen, Ya-Nan Zhang, McGurran, Hugo, Stormmesand, Jochem, Breeuwsma, Nicole, Sluiter, Arja, Juan Zhao, Swaab, Dick, and Ai-Min Bao
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ALZHEIMER'S disease ,AMYLOID beta-protein precursor ,LABORATORY mice ,ANIMAL disease models ,HIPPOCAMPUS (Brain) - Abstract
Introduction: Epidemiological studies show that women have a higher prevalence of Alzheimer's disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1M146V, APPSwe, and TauP301L show sex differences in b-amyloid (Ab) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17b-estradiol (E2) may regulate the expression of EGR1 and AChE. Methods: We first sacrificed male and female 3xTg-AD mice at 3-4, 7-8, and 11-12 months and measured the levels of Ab, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Ab and intracellular EGR1 and AChE. Results: Female 3xTg-AD mice had higher levels of Ab compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Ab and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Ab(1-42) was significantly decreased while intracellular EGR1 and AChE expression were elevated. Discussion: This data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Ab. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Ab(1-42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Changes of hypocretin (orexin) system in schizophrenia
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Tingting Mou, Rolf Fronczek, Dick F. Swaab, Kangyu Jin, Jinfeng Duan, Haimei Li, Weijuan Xu, Ai-Min Bao, Jing Lu, Jin-Hui Li, Manli Huang, and Netherlands Institute for Neuroscience (NIN)
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Adult ,Male ,medicine.medical_specialty ,Prefrontal Cortex ,superior frontal gyrus ,Neurotransmission ,cerebrospinal fluid ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Sex Factors ,Orexin Receptors ,Internal medicine ,mental disorders ,medicine ,Humans ,hypothalamus ,Receptor ,orexin, hypocretin receptor ,plasma ,Orexins ,hypocretin receptor ,business.industry ,Middle Aged ,medicine.disease ,030227 psychiatry ,Orexin ,schizophrenia ,Psychiatry and Mental health ,Endocrinology ,Superior frontal gyrus ,orexin ,nervous system ,Schizophrenia ,Hypothalamus ,Female ,Autopsy ,hypocretin ,business ,030217 neurology & neurosurgery ,psychological phenomena and processes ,Hypocretin orexin ,Regular Articles - Abstract
Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.
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- 2021
13. The human hypothalamus in mood disorders: The HPA axis in the center
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Dick F. Swaab, Ai-Min Bao, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,Neuropeptide ,Amygdala ,lcsh:RC321-571 ,GABA ,03 medical and health sciences ,0302 clinical medicine ,Sex differences ,medicine ,Prefrontal cortex ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Depression (differential diagnoses) ,Articles from the Special Issue on Emotion and mood disorders: from molecular mechanisms to neuronal circuits ,Edited by Jiang-Ning Zhou ,General Neuroscience ,Cognition ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Habenula ,Mood disorders ,Hypothalamus ,Glutamate ,Psychology ,Neuroscience ,The hypothalamo-pituitary-adrenal axis ,030217 neurology & neurosurgery - Abstract
There are no specific structural neuropathological hallmarks found in the brain of mood disorders. Instead, there are molecular, functional and structural alterations reported in many brain areas. The neurodevelopmental underpinning indicated the presence of various genetic and developmental risk factors. The effect of genetic polymorphisms and developmental sequalae, some of which may start in the womb, result in functional changes in a network mediated by neurotransmitters and neuropeptides, which make the emotion- and stress-related brain systems more vulnerable to stressful events. This network of stress-related neurocircuits consists of, for instance, brainstem nuclei, the amygdala, habenula, prefrontal cortex and hypothalamus. Various nuclei of the hypothalamus form indeed one of the crucial hubs in this network. This structure concerns not only the hypothalamo-pituitary-adrenal (HPA) axis that integrate the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of depression, such as disordered day-night rhythm, lack of reward feelings, disturbed eating, sex, and disturbed cognitive functions. The present review will focus on the changes in the human hypothalamus in depression, with the HPA axis in the center. We will discuss the inordinate network of neurotransmitters and neuropeptides involved, with the hope to find the most vulnerable neurobiological systems and the possible development of tailor-made treatments for mood disorders in the future. Keywords: The hypothalamo-pituitary-adrenal axis, Glutamate, GABA, Neuropeptide, Sex differences
- Published
- 2019
14. Activation of the Brain to Postpone Dementia: A Concept Originating from Postmortem Human Brain Studies
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Dick F. Swaab, Ai-Min Bao, Qiong-Bin Zhu, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,medicine.medical_specialty ,Neurology ,Physiology ,Models, Neurological ,Physical exercise ,Review ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Animals ,Humans ,Medicine ,Dementia ,Cognitive decline ,Cognitive reserve ,business.industry ,General Neuroscience ,Neurodegeneration ,Brain ,General Medicine ,Human brain ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Alzheimer’s disease (AD) is characterized by decreased neuronal activity and atrophy, while hyperactivity of neurons seems to make them resistant to aging and neurodegeneration, a phenomenon which we have paraphrased as ‘use it or lose it’. Our hypothesis proposes that (1) during their functioning, neurons are damaged; (2) accumulation of damage that is not repaired is the basis of aging; (3) the vulnerability to AD is determined by the genetic background and the balance between the amount of damage and the efficiency of repair, and (4) by stimulating the brain, repair mechanisms are stimulated and cognitive reserve is increased, resulting in a decreased rate of aging and risk for AD. Environmental stimulating factors such as bilingualism/multilingualism, education, occupation, musical experience, physical exercise, and leisure activities have been reported to reduce the risk of dementia and decrease the rate of cognitive decline, although methodological problems are present.
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- 2019
15. Human Brain Slice Culture
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Ronald W.H. Verwer, Sabina Luchetti, Rawien Balesar, Dick F. Swaab, Ai-Min Bao, Jiang-Ning Zhou, Xin-Rui Qi, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,medicine.medical_specialty ,Neurology ,Physiology ,Review ,Tissue Culture Techniques ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,Humans ,Depression (differential diagnoses) ,Brain-derived neurotrophic factor ,Brain Diseases ,business.industry ,General Neuroscience ,Brain ,General Medicine ,Human brain ,030104 developmental biology ,medicine.anatomical_structure ,Neuropsychiatric disorder ,Cell culture ,Brain bank ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
- Published
- 2019
16. Brain transcriptional regulatory architecture and schizophrenia etiology converge between East Asian and European ancestral populations
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Richard F. Kopp, Yi Jiang, Duan F, Yan Xia, Faming Wang, Jufang Huang, Zhilin Ning, Maoyu Li, Wenying Qiu, Jiapei Dai, Xuhua Yan, Chunxia Ma, Shuhua Xu, Beisha Tang, Chao Chen, Sihan Liu, Liz Kuney, Ai-Min Bao, Chunyu Liu, and Yu Chen
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Transcriptome ,Linkage disequilibrium ,Evolutionary biology ,Expression quantitative trait loci ,Quantitative trait locus ,Biology ,Gene ,Allele frequency ,Genetic architecture ,Genetic association - Abstract
Understanding the genetic architecture of gene expression and splicing in human brain is critical to unlocking the mechanisms of complex neuropsychiatric disorders like schizophrenia (SCZ). Large-scale brain transcriptomic studies are based primarily on populations of European (EUR) ancestry. The uniformity of mono-racial resources may limit important insights into the disease etiology. Here, we characterized brain transcriptional regulatory architecture of East Asians (EAS; n=151), identifying 3,278 expression quantitative trait loci (eQTL) and 4,726 spliceQTL (sQTL). Comparing these to PsychENCODE/BrainGVEX confirmed our hypothesis that the transcriptional regulatory architecture in EAS and EUR brains align. Furthermore, distinctive allelic frequency and linkage disequilibrium impede QTL translation and gene-expression prediction accuracy. Integration of eQTL/sQTL with genome-wide association studies reveals common and novel SCZ risk genes. Pathway-based analyses showing shared SCZ biology point to synaptic and GTPase dysfunction as a prospective pathogenesis. This study elucidates the transcriptional landscape of the EAS brain and emphasizes an essential convergence between EAS and EUR populations.
- Published
- 2021
17. Histamine H1 receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice
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Lu Wang, Kuo Zhang, Xiangnan Zhang, Jingyu Yang, Weiwei Hu, Xiao-Dong Wang, Dick F. Swaab, Yi Wang, Li Cheng, Yanrong Zheng, Yujing Wang, Cenglin Xu, Zhong Chen, Dadao An, Ai-Min Bao, Lei Jiang, Yi-xin Xu, Yu-Dong Zhou, Shumin Duan, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,Science ,General Physics and Astronomy ,Histamine H1 receptor ,behavioral disciplines and activities ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Cholinergic neuron ,Receptor ,Prefrontal cortex ,Basal forebrain ,Multidisciplinary ,Sensory gating ,business.industry ,General Chemistry ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Schizophrenia ,behavior and behavior mechanisms ,Cholinergic ,business ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.
- Published
- 2021
18. Direct Involvement of Androgen Receptor in Oxytocin Gene Expression
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Dan Dai, Dick F. Swaab, Ai-Min Bao, Rawien Balesar, Qiao-Chu Li, Shaohua Hu, Qiong-Bin Zhu, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,medicine.medical_specialty ,Cytoplasm ,Immunocytochemistry ,Hypothalamus ,Gene Expression ,Oxytocin ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cell Line, Tumor ,Gene expression ,medicine ,Journal Article ,Humans ,Testosterone ,RNA, Messenger ,Receptor ,Promoter Regions, Genetic ,Pharmacology ,Cell Nucleus ,Neurons ,Mood Disorders ,medicine.disease ,Immunohistochemistry ,Androgen receptor ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,Mood disorders ,Receptors, Androgen ,Original Article ,Psychopharmacology ,Psychology ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and then released into different brain areas, may play a crucial role in various behaviors and neuropsychiatric disorders, including depression. Testosterone has been proposed by clinical studies to have the opposite effect of oxytocin in these disorders. We began by studying, in the postmortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls, the expression of OXT in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) by means of double labeling ICC. Subsequently, the regulatory effect of AR on OXT gene expression was studied in vitro. We found a higher expression of PVN OXT in the mood disorder patients than in the control subjects, and observed a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. In addition, a significant decrease in OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with testosterone. A further potential androgen-responsive element in the human OXT gene promotor was revealed by electrophoretic mobility shift assays and co-transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that AR mediated the down-regulation of OXT gene expression. These results suggest that the fact that OXT and testosterone appear to have opposite effects in neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.Neuropsychopharmacology accepted article preview online, 27 April 2017. doi:10.1038/npp.2017.76.
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- 2017
19. Sexually Dimorphic Changes of Hypocretin (Orexin) in Depression
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Rolf Fronczek, Jing Lu, Xue-Yan Wu, Rawien Balesar, Qiong-Bin Zhu, Shaohua Hu, Juan Zhao, Ai-Min Bao, Dick F. Swaab, and Netherlands Institute for Neuroscience (NIN)
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Male ,Bipolar Disorder ,Corticotropin-Releasing Hormone ,lcsh:Medicine ,Rats, Sprague-Dawley ,Corticotropin-releasing hormone ,0302 clinical medicine ,Orexin Receptors ,Cortex (anatomy) ,Prefrontal cortex ,Aged, 80 and over ,Sex Characteristics ,lcsh:R5-920 ,Depression ,General Medicine ,Middle Aged ,Immunohistochemistry ,Orexin receptor ,medicine.anatomical_structure ,Hypothalamus ,Female ,lcsh:Medicine (General) ,psychological phenomena and processes ,Research Paper ,medicine.medical_specialty ,Hypocretin ,Prefrontal Cortex ,Gyrus Cinguli ,General Biochemistry, Genetics and Molecular Biology ,Hypocretin receptors ,03 medical and health sciences ,Internal medicine ,mental disorders ,medicine ,Animals ,Humans ,RNA, Messenger ,Protein Precursors ,Anterior cingulate cortex ,Aged ,Depressive Disorder, Major ,Orexins ,business.industry ,lcsh:R ,Sex difference ,Rats ,030227 psychiatry ,Orexin ,Dorsolateral prefrontal cortex ,Disease Models, Animal ,Endocrinology ,nervous system ,Corticosterone ,business ,030217 neurology & neurosurgery - Abstract
Background Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects. Methods We quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat. Results i) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats. Conclusions The clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies., Highlights • Hypocretin (orexin) changes were studied in human postmortem brain in depression. • A clear sex-related change was found in the hypothalamic hypocretin-1-immunoreactivity in depression. • A rat depression model did not reflect the changes in the hypocretin system in the human brain in depression. The stress systems of depressed patients are put into a higher gear by genetic and developmental factors. Over-reaction of these systems to stressful environmental situations makes people vulnerable to depression and suicide. This is the first postmortem study on changes in a relatively novel stress system in depression, consisting of the hypothalamic hypocretin neurons and hypocretin receptors in the prefrontal cortex. A clear sex-related change was found in the hypothalamic hypocretin-1-immunoreactivity in depression. Evaluation of the hypocretin system in a frequently used depression animal model, i.e. chronic unpredictable mild stress rats, did not replicate changes found in the hypocretin systems in the human brain in depression.
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- 2017
20. Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression
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Qiong-Bin Zhu, Manli Huang, Dick F. Swaab, Rawien Balesar, Ai-Min Bao, Safar Farajnia, Jing Lu, Xue-Yan Wu, and Netherlands Institute for Neuroscience (NIN)
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Male ,0301 basic medicine ,medicine.medical_specialty ,Vasopressin ,endocrine system ,Histology ,animal structures ,Glutamate decarboxylase ,In situ hybridization ,Biology ,Statistics, Nonparametric ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Internal medicine ,medicine ,Journal Article ,Humans ,RNA, Messenger ,Circadian rhythm ,gamma-Aminobutyric Acid ,Depression (differential diagnoses) ,Aged ,Aged, 80 and over ,Depression ,Glutamate Decarboxylase ,Suprachiasmatic nucleus ,General Neuroscience ,Arginine Vasopressin ,030104 developmental biology ,Endocrinology ,nervous system ,Hypothalamus ,GABAergic ,Female ,Suprachiasmatic Nucleus ,sense organs ,Erratum ,Anatomy ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists - Abstract
In depression, disrupted circadian rhythms reflect abnormalities in the central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Although many SCN neurons are said to be GABAergic, it was not yet known whether and how SCN GABA changes occur in the SCN in depression. We, therefore, studied GABA in the SCN in relation to the changes in arginine vasopressin (AVP), which is one of the major SCN output systems. Postmortem hypothalamus specimens of 13 subjects suffering from depression and of 13 well-matched controls were collected. Quantitative immunocytochemistry was used to analyze the protein levels of glutamic acid decarboxylase (GAD)65/67 and AVP, and quantitative in situ hybridization was used to measure transcript levels of GAD67 in the SCN. There were a significant 58% increase of SCN GAD65/67-ir and a significant 169% increase of SCN GAD67-mRNA in the depression group. In addition, there were a significant 253% increase of AVP-ir in female depression subjects but not in male depression patients. This sex difference was supported by a re-analysis of SCN AVP-ir data of a previous study of our group. Moreover, SCN-AVP-ir showed a significant negative correlation with age in the control group and in the male, but not in the female depression group. Given the crucial role of GABA in mediating SCN function, our finding of increased SCN GABA expression may significantly contribute to the disordered circadian rhythms in depression. The increased SCN AVP-ir in female-but not in male-depression patients-may reflect the higher vulnerability for depression in women.
- Published
- 2017
21. Progress in Human Brain Banking in China
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Chao Ma, Xiao-Xin Yan, Dick F. Swaab, Ai-Min Bao, and Netherlands Institute for Neuroscience (NIN)
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medicine.medical_specialty ,China ,Neurology ,Physiology ,business.industry ,General Neuroscience ,Pain medicine ,MEDLINE ,Brain ,General Medicine ,Human physiology ,Human brain ,Tissue Banks ,medicine.anatomical_structure ,Editorial ,Anesthesiology ,Medicine ,Humans ,business ,Intensive care medicine - Published
- 2019
22. Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease
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Ai-Min Bao, Shu-Han Huang, Arja A. Sluiter, Si-Yang Yu, Yi Shen, Juan Zhao, Dick F. Swaab, Qiong-Bin Zhu, Yu-Ting Hu, Joost Verhaagen, Xin-Lu Chen, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,medicine.medical_specialty ,endocrine system ,EGR1 ,Mice, Transgenic ,Biology ,Pathology and Forensic Medicine ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,medicine ,Animals ,Humans ,Electrophoretic mobility shift assay ,RNA, Messenger ,Promoter Regions, Genetic ,Prefrontal cortex ,Transcription factor ,Research Articles ,Early Growth Response Protein 1 ,Messenger RNA ,General Neuroscience ,Brain ,Promoter ,Acetylcholinesterase ,Frontal Lobe ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,chemistry ,Disease Progression ,Cholinergic ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD. This article is protected by copyright. All rights reserved.
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- 2019
23. MicroRNA-132 and early growth response-1 in nucleus basalis of Meynert during the course of Alzheimer's disease
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Yu-Ting Hu, Rawien Balesar, Koen Bossers, Ronald W.H. Verwer, Dick F. Swaab, Juan Zhao, Qiong-Bin Zhu, Unga A. Unmehopa, Ai-Min Bao, and Netherlands Institute for Neuroscience (NIN)
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Male ,0301 basic medicine ,Apolipoprotein E ,Pathology ,medicine.medical_specialty ,Biology ,Nucleus basalis ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,medicine ,Humans ,Single-Blind Method ,Prefrontal cortex ,Aged ,Early Growth Response Protein 1 ,Aged, 80 and over ,Neurons ,Neurodegeneration ,Middle Aged ,medicine.disease ,Choline acetyltransferase ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Basal Nucleus of Meynert ,Disease Progression ,Cholinergic ,Female ,Neurology (clinical) ,Alzheimer's disease ,Nucleus ,030217 neurology & neurosurgery - Abstract
The cholinergic nucleus basalis of Meynert, which is important for memory functions, shows neuronal activation ('up-phase') during the early stages of Alzheimer's disease and neurodegeneration ('down-phase') in later stages of Alzheimer's disease. MicroRNA-132 (miR-132) and the transcription factor early growth response-1 (EGR1) were proposed as possible candidate molecules regulating such an up-down activity pattern of the nucleus basalis of Meynert during the course of Alzheimer's disease, as they both show this up-down pattern of expression in the prefrontal cortex during the course of Alzheimer's disease. Not only do these two molecules stimulate synaptic activity and plasticity, they are also involved in Alzheimer's disease pathology and might, in addition, affect cholinergic function. In the nucleus basalis of Meynert, we investigated the expression of miR-132 and EGR1 along the entire course of Alzheimer's disease. Forty-nine post-mortem nucleus basalis of Meynert samples were studied, ranging from non-demented controls (Braak stage = 0) to late Alzheimer's disease patients (Braak stage = VI), and from clinical Reisberg scale 1 to 7. Each Braak stage contained seven samples, that were all well matched for confounding factors, i.e. age (range 58-91), sex, post-mortem delay, cerebrospinal fluid pH (as a measure for agonal state), APOE genotype, clock time of death, tissue fixation time, and tissue storage time. The alterations of these two molecules were studied over the course of Alzheimer's disease in relation to the expression of 4G8-stained amyloid-β, hyperphosphorylated tau stained by antibody AT8, neuronal fibrillary tangles and neuropil threads stained by silver, and in relation to alterations in choline acetyltransferase. We found that the expression of miR-132 and EGR1 in the nucleus basalis of Meynert was quite stable during the early stages of Alzheimer's disease and decreased significantly only during late Alzheimer's disease stages. In addition, miR-132 and EGR1 showed a significant positive correlation with choline acetyltransferase expression (r = 0.49, P < 0.001 and r = 0.61, P < 0.001), while choline acetyltransferase expression showed a significantly negative correlation with hyperphosphorylated tau (r = -0.33, P = 0.021) but no correlation with 4G8-stained amyloid-β. From the functional changes of miR-132 and EGR1 along the course of Alzheimer's disease we conclude: (i) that these two molecules may play a role in keeping the cholinergic function intact in early Alzheimer's disease stages; and (ii) that these molecules may contribute to the late neurodegeneration of this cholinergic nucleus.
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- 2016
24. Author response: ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines
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Shu-Xia Cao, Ying Zhang, Xing-Yue Hu, Bin Hong, Peng Sun, Hai-Yang He, Hong-Yan Geng, Ai-Min Bao, Shu-Min Duan, Jian-Ming Yang, Tian-Ming Gao, Hong Lian, and Xiao-Ming Li
- Published
- 2018
25. Quantification of Tyrosine Hydroxylase and ErbB4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin
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Arja A. Sluiter, Rawien Balesar, Zheng Fang, Qingbin Zhu, Dick F. Swaab, Jochem Stormmesand, Joop Van Heerikhuize, Ai-Min Bao, Lei Guo, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,Male ,medicine.medical_specialty ,Bipolar Disorder ,Receptor, ErbB-4 ,Tyrosine 3-Monooxygenase ,Physiology ,Method ,Biology ,Sensitivity and Specificity ,03 medical and health sciences ,0302 clinical medicine ,Neuromelanin ,Internal medicine ,mental disorders ,medicine ,Image Processing, Computer-Assisted ,Humans ,Bipolar disorder ,Receptor ,ERBB4 ,Aged ,Aged, 80 and over ,Melanins ,Neurons ,Depressive Disorder, Major ,Microscopy ,Tyrosine hydroxylase ,General Neuroscience ,Spectrum Analysis ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Staining ,030104 developmental biology ,Endocrinology ,Major depressive disorder ,Locus coeruleus ,Female ,Locus Coeruleus ,030217 neurology & neurosurgery - Abstract
The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients-thus validating the method-but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.
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- 2018
26. ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines
- Author
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Xing-Yue Hu, Peng Sun, Xiao-Ming Li, Bin Hong, Shu-Xia Cao, Tian-Ming Gao, Jian-Ming Yang, Hong-Yan Geng, Shumin Duan, Ai-Min Bao, Ying Zhang, Hai-Yang He, and Hong Lian
- Subjects
0301 basic medicine ,Adrenergic Neurons ,Bipolar Disorder ,Receptor, ErbB-4 ,Mouse ,Lithium (medication) ,Dopamine ,Action Potentials ,Pathogenesis ,ErbB4 ,Mice ,Norepinephrine ,0302 clinical medicine ,Catecholamines ,Biology (General) ,Phosphorylation ,Receptor ,ERBB4 ,Catecholaminergic ,Behavior, Animal ,General Neuroscience ,General Medicine ,NMDA receptor ,Medicine ,Locus Coeruleus ,medicine.symptom ,Mania ,Research Article ,medicine.drug ,Psychosis ,medicine.medical_specialty ,Tyrosine 3-Monooxygenase ,QH301-705.5 ,Science ,Green Fluorescent Proteins ,Biology ,Lithium ,Catechol O-Methyltransferase ,behavioral disciplines and activities ,Receptors, N-Methyl-D-Aspartate ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,mania ,Delusion ,Internal medicine ,mental disorders ,medicine ,Animals ,Bipolar disorder ,General Immunology and Microbiology ,Integrases ,Body Weight ,Excitatory Postsynaptic Potentials ,Correction ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,nervous system ,noradrenergic neuron ,Locus coeruleus ,Neuroscience ,030217 neurology & neurosurgery ,Gene Deletion - Abstract
Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, Erbb4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder., eLife digest Bipolar disorder is a mental illness that affects roughly 1 in 100 people worldwide. It features periods of depression interspersed with episodes of mania – a state of delusion, heightened excitation and increased activity. Evidence suggests that changes in a brain region called the locus coeruleus contribute to bipolar disorder. Cells within this area produce a chemical called norepinephrine, whose levels increase during mania and decrease during depression. But it is unclear exactly how norepinephrine-producing cells, also known as noradrenergic cells, contribute to bipolar disorder. The answer may lie in a protein called ErbB4, which is found within the outer membrane of many noradrenergic neurons. ErbB4 is active in both the developing and adult brain, and certain people with bipolar disorder have mutations in the gene that codes for the protein. Might changes in ErbB4 disrupt the activity of noradrenergic neurons? And could these changes increase the risk of bipolar disorder? To find out, Cao, Zhang et al. deleted the gene for ErbB4 from noradrenergic neurons in the locus coeruleus of mice. The mutant mice showed mania-like behaviors: compared to normal animals, they were hyperactive, less anxious, and consumed more of a sugary solution. Treating the mice with lithium, a medication used in bipolar disorder, reversed these changes and made the rodents behave more like non-mutant animals. Further experiments revealed that noradrenergic neurons in the mutant mice showed increased spontaneous activity. These animals also had more of the chemicals noradrenaline and dopamine in the fluid circulating around their brains and spinal cords. The results thus suggest that losing ErbB4 enhances the spontaneous firing of noradrenergic neurons in the locus coeruleus. This increases release of noradrenaline and dopamine, which in turn leads to mania-like behaviors. Future research should examine whether drugs that target ErbB4 could treat mania and improve the lives of people with bipolar disorder and related conditions.
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- 2018
27. Early growth response-1 stimulates acetylcholinesterase during the course of Alzheimer's disease
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Yu-Ting Hu, Xin-Lu Chen, Dick F. Swaab, Ai-Min Bao, Shu-Han Huang, Hugo McGurran, and Jackson Boonstra
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medicine.medical_specialty ,chemistry.chemical_compound ,Endocrinology ,chemistry ,business.industry ,General Neuroscience ,Internal medicine ,Early growth response 1 ,medicine ,Disease ,business ,Acetylcholinesterase - Published
- 2019
28. Membrane estrogen receptor stimulation of corticotropin-releasing hormone expression in a nerve cell line
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Zhong Ren, Zheng Fang, Yi Shen, Juan-Li Wu, Lei Guo, Yang He, Yang-Jian Qi, Hong Tan, Man-Li Huang, and Ai-Min Bao
- Subjects
medicine.medical_specialty ,Membrane estrogen receptor ,Corticotropin-releasing hormone ,Endocrinology ,Chemistry ,Cell culture ,General Neuroscience ,Internal medicine ,medicine ,Stimulation - Published
- 2019
29. Decreased NOS1 expression in the anterior cingulate cortex in depression
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Shang-Feng Gao, Xin-Rui Qi, Rawien Balesar, Dick F. Swaab, Juan Zhao, Ai-Min Bao, Other Research, Medical Biology, and Netherlands Institute for Neuroscience (NIN)
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Male ,medicine.medical_specialty ,Cognitive Neuroscience ,NOS1 ,Nitric Oxide Synthase Type I ,Biology ,Neurotransmission ,Nitric Oxide ,Gyrus Cinguli ,Nitric oxide ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Glutamatergic ,Internal medicine ,medicine ,Humans ,GABAergic Neurons ,Anterior cingulate cortex ,Depressive Disorder, Major ,Pyramidal Cells ,Glutamate receptor ,Nitric oxide synthase ,medicine.anatomical_structure ,Endocrinology ,chemistry ,nervous system ,biology.protein ,GABAergic ,Female ,human activities - Abstract
Decreased function of the anterior cingulate cortex (ACC) is crucially involved in the pathogenesis of depression. A key role of nitric oxide (NO) has also been proposed. We aimed to determine the NO content in the cerebrospinal fluid (CSF) and the expression of NO synthase (NOS) isoforms, that is, NOS1, NOS2, and NOS3 in the ACC in depression. In depressive patients, CSF-NOx levels (the levels of the NO metabolites nitrite and nitrate) were significantly decreased (P = 0.007), indicating a more general decrease of NO production in this disorder. This agreed with a trend toward lower NOS1-mRNA levels (P = 0.083) and a significant decrease of NOS1-immunoreactivity (ir) (P = 0.043) in ACC. In controls, there was a significant positive correlation between ACC-NOS1-ir cell densities and their CSF-NOx levels. Furthermore, both localization of NOS1 in pyramidal neurons that are known to be glutamatergic and co-localization between NOS1 and GABAergic neurons were observed in human ACC. The diminished ACC-NOS1 expression and decreased CSF-NOx levels may be involved in the alterations of ACC activity in depression, possibly by affecting glutamatergic and GABAergic neurotransmission.
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- 2013
30. Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study
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Manli Huang, Jingkai Chen, Bradley S. Peterson, Hong-li Qi, Dongrong Xu, Jianbo Lai, Ai-min Bao, Weijuan Xu, Chan-Chan Hu, Shu-lan Li, Shaohua Hu, Yi Xu, Weihua Zhou, Ning Wei, and Jianbo Hu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Bipolar Disorder ,Adolescent ,Trail Making Test ,behavioral disciplines and activities ,Article ,law.invention ,03 medical and health sciences ,Quetiapine Fumarate ,0302 clinical medicine ,Randomized controlled trial ,Wisconsin Card Sorting Test ,Double-Blind Method ,law ,Internal medicine ,mental disorders ,Medicine ,Humans ,Effects of sleep deprivation on cognitive performance ,Bipolar disorder ,Psychiatry ,Multidisciplinary ,business.industry ,medicine.disease ,Transcranial Magnetic Stimulation ,030227 psychiatry ,Treatment Outcome ,Quetiapine ,Female ,business ,030217 neurology & neurosurgery ,Stroop effect ,medicine.drug ,Antipsychotic Agents - Abstract
The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.
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- 2016
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31. Functional Increase of Brain Histaminergic Signaling in Huntington's Disease
- Author
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Ai-Min Bao, Raymund A.C. Roos, N. Ahmad Aziz, Ling Shan, Daniel J. van Wamelen, Dick F. Swaab, and Jasper J. Anink
- Subjects
medicine.medical_specialty ,Histamine N-methyltransferase ,General Neuroscience ,Histaminergic ,Caudate nucleus ,Biology ,medicine.disease ,Histidine decarboxylase ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Histamine receptor ,Endocrinology ,chemistry ,Huntington's disease ,Internal medicine ,medicine ,Neurology (clinical) ,Receptor ,Histamine - Abstract
To evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, we assessed mRNA levels of histidine decarboxylase (HDC), volume of and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed histamine N-methyltransferase (HMT) and histamine receptor (H(1) R, H(2) R and H(3) R) mRNA levels in the inferior frontal gyrus (IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by real-time polymerase chain reaction. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). The levels of HDC mRNA (P = 0.046), IFG HMT (P < 0.001), H(1) R (P < 0.001) and H(3) R mRNA levels (P = 0.011) were increased, while CN H(2) R and H(3) R mRNA levels were decreased (P = 0.041, P = 0.009). In HD patients, we observed a positive correlation between IFG H(3) R mRNA levels and CAG repeat length (P = 0.024) and negative correlations between age at onset of disease and IFG HMT (P = 0.015) and H(1) R (P = 0.021) mRNA levels. These findings indicate a functional increase in brain histaminergic signaling in HD, and provide a rationale for the use of histamine receptor antagonists.
- Published
- 2010
32. Colocalization of corticotropin-releasing hormone and oestrogen receptor-α in the paraventricular nucleus of the hypothalamus in mood disorders
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Jiang-Ning Zhou, Andon Hestiantoro, Ai-Min Bao, Eus J.W. Van Someren, Dick F. Swaab, Other Research, and Medical Biology
- Subjects
Male ,Hypothalamo-Hypophyseal System ,endocrine system ,medicine.medical_specialty ,Corticotropin-Releasing Hormone ,Thalamus ,Pituitary-Adrenal System ,Corticotropin-releasing hormone ,Internal medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Aged ,Cell Nucleus ,Neurons ,Staining and Labeling ,Mood Disorders ,Estrogen Receptor alpha ,Brain ,Colocalization ,Organ Size ,Middle Aged ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Mood disorders ,Hypothalamus ,Major depressive disorder ,Female ,Neurology (clinical) ,Psychology ,Nucleus ,hormones, hormone substitutes, and hormone antagonists ,Hypothalamic–pituitary–adrenal axis ,Paraventricular Hypothalamic Nucleus - Abstract
Oestrogens may modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH) neurons of the human hypothalamic paraventricular nucleus (PVN). Brains of 13 subjects ranging in age between 45 and 79 years suffering from major depression/major depressive disorder (eight cases) or bipolar disorder (five cases) and of 13 controls, matched for sex, age, brain weight, post-mortem delay, fixation time and season and clock time at death, were studied with double-label immunocytochemistry. The total number of CRH-immunoreactive (IR) neurons, CRH neurons that colocalized ORalpha in the neuronal nucleus and the number of only nuclear ORalpha-containing neurons in the PVN were measured using an image analysis system. In addition, the volume of the PVN delineated on the basis of CRH neurons was determined. It was found that the total number of CRH-IR neurons in patients with mood disorders was nearly 1.7 times higher than in controls (P = 0.034). A novel finding was that the total number of CRH-IR neurons and the number of CRH-nuclear ORalpha double-staining neurons in the PVN were strongly correlated both in controls and in patients with mood disorders (P < 0.001 and P = 0.022, respectively). The ratio of the CRH-nuclear-ORalpha double-staining neurons to the total CRH-IR neurons in patients with mood disorders was similar to that in the controls (P = 0.448). The volume of the sub-region of the PVN that was delineated on the basis of CRH neurons was significantly larger in patients with mood disorders than in controls (P = 0.022). Another novel finding was the large population of extra-hypothalamic CRH neurons that was found in the thalamus. In summary, oestrogens may directly influence CRH neurons in the human PVN. The increased numbers of neurons expressing CRH in mood disorders is accompanied by increased ORalpha colocalization in the nucleus of these neurons. These changes seem to be trait- rather than state-related.
- Published
- 2005
33. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases
- Author
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Dick F. Swaab, Daniel J. van Wamelen, Michel A. Hofman, Ling Shan, Ai-Min Bao, Eus J.W. Van Someren, Netherlands Institute for Neuroscience (NIN), Medical psychology, Integrative Neurophysiology, Neuroscience Campus Amsterdam - Attention & Cognition, and Neuroscience Campus Amsterdam - Neurodegeneration
- Subjects
medicine.medical_specialty ,Short Note ,Gene Expression ,In situ hybridization ,Biology ,Diurnal fluctuations ,chemistry.chemical_compound ,SDG 3 - Good Health and Well-being ,Alzheimer Disease ,Physiology (medical) ,Internal medicine ,Gene expression ,medicine ,Humans ,Histidine ,Circadian rhythm ,In Situ Hybridization ,Histamine Production ,histidine decarboxylase ,Hydantoins ,Neurodegenerative Diseases ,Parkinson Disease ,medicine.disease ,Histidine decarboxylase ,histamine ,Circadian Rhythm ,Huntington Disease ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Case-Control Studies ,Hypothalamic Area, Lateral ,neurodegenerative disorders ,tuberomammillary nucleus ,Neurology (clinical) ,Alzheimer's disease ,Tuberomammillary nucleus ,Histamine - Abstract
Neuronal histamine shows diurnal rhythms in rodents and plays a major role in the maintenance of vigilance. No data are available on its diurnal fluctuation in humans, either in health or in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD), or Huntington disease (HD), all of which are characterized by sleep-wake disturbances.Quantitative in situ hybridization was used to study the mRNA expression of histidine decarboxylase (HDC), the key enzyme of histamine production in the tuberomammillary nucleus (TMN) in postmortem human hypothalamic tissue, obtained from 33 controls and 31 patients with a neurodegenerative disease-PD (n = 15), AD (n = 9), and HD (n = 8)-and covering the full 24-h cycle with respect to clock time of death.HDC-mRNA levels in controls were found to be significantly higher during the daytime than at night (e.g., 08:01-20:00 versus 20:01-08:00, P = 0.004). This day-night fluctuation was markedly different in patients with neurodegenerative diseases.The diurnal fluctuation of HDC-mRNA expression in human TMN supports a role for neuronal histamine in regulating day-night rhythms. Future studies should investigate histamine rhythm abnormalities in neurodegenerative disorders.Shan L; Hofman MA; van Wamelen DJ; Van Someren EJW; Bao AM; Swaab DF. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases.
- Published
- 2012
34. Erratum to: Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression
- Author
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Xueyan Wu, Rawien Balesar, Jing Lu, Sahar Farajnia, Qiongbin Zhu, Manli Huang, Ai-Min Bao, and Dick F. Swaab
- Subjects
endocrine system ,animal structures ,Histology ,Depression ,General Neuroscience ,Sex difference ,Suprachiasmatic nucleus ,GABA ,nervous system ,Original Article ,Arginine vasopressin ,sense organs ,Anatomy ,hormones, hormone substitutes, and hormone antagonists - Abstract
In depression, disrupted circadian rhythms reflect abnormalities in the central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Although many SCN neurons are said to be GABAergic, it was not yet known whether and how SCN GABA changes occur in the SCN in depression. We, therefore, studied GABA in the SCN in relation to the changes in arginine vasopressin (AVP), which is one of the major SCN output systems. Postmortem hypothalamus specimens of 13 subjects suffering from depression and of 13 well-matched controls were collected. Quantitative immunocytochemistry was used to analyze the protein levels of glutamic acid decarboxylase (GAD)65/67 and AVP, and quantitative in situ hybridization was used to measure transcript levels of GAD67 in the SCN. There were a significant 58% increase of SCN GAD65/67-ir and a significant 169% increase of SCN GAD67-mRNA in the depression group. In addition, there were a significant 253% increase of AVP-ir in female depression subjects but not in male depression patients. This sex difference was supported by a re-analysis of SCN AVP-ir data of a previous study of our group. Moreover, SCN-AVP-ir showed a significant negative correlation with age in the control group and in the male, but not in the female depression group. Given the crucial role of GABA in mediating SCN function, our finding of increased SCN GABA expression may significantly contribute to the disordered circadian rhythms in depression. The increased SCN AVP-ir in female—but not in male-depression patients—may reflect the higher vulnerability for depression in women. Electronic supplementary material The online version of this article (doi:10.1007/s00429-017-1442-y) contains supplementary material, which is available to authorized users.
- Published
- 2017
35. Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder
- Author
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Hui-Chun Li, Xin-Yan Fu, Li-Gen Shi, Zheng Lin, Yunrong Lu, Jian-Hong Luo, Zhaopin Wang, Xue-Yan Wu, Yan Jiang, Wei-Bo Liu, Xiao-Juan Weng, Juan-Li Wu, and Ai-Min Bao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Glycine ,Glutamic Acid ,Gamma - aminobutyric acid ,Major depressive disorder ,gamma-Aminobutyric acid ,Nitric oxide ,Young Adult ,chemistry.chemical_compound ,Internal medicine ,Aspartic acid ,medicine ,Humans ,Amino Acids ,gamma-Aminobutyric Acid ,Aged ,chemistry.chemical_classification ,Aspartic Acid ,Depressive Disorder, Major ,Fluoxetine ,Glutamic acid ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Amino acid ,Psychiatry and Mental health ,Endocrinology ,chemistry ,Antidepressant ,Female ,Biomarkers ,Research Article ,Follow-Up Studies ,medicine.drug - Abstract
Background Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder. Methods Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months’ antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects. Results The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds. Conclusion These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.
- Published
- 2014
36. Effects of curcumin on glucose metabolism in the brains of rats subjected to chronic unpredictable stress: a 18 F-FDG micro-PET study
- Author
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Li-Gen Shi, Chuantao Zuo, Ai-Min Bao, Weijun Tang, Yunrong Lu, Zheng Lin, Lei Xu, Jing Lu, Hua Hu, and Jin-Hui Li
- Subjects
Male ,medicine.medical_specialty ,Curcumin ,Sucrose ,Carbohydrate metabolism ,Brain mapping ,Open field ,Rats, Sprague-Dawley ,Random Allocation ,chemistry.chemical_compound ,Fluorodeoxyglucose F18 ,Stress, Physiological ,Internal medicine ,Animals ,Medicine ,Fluorodeoxyglucose ,Brain Mapping ,Behavior, Animal ,business.industry ,Body Weight ,Brain ,General Medicine ,Antidepressive Agents ,Rats ,Cortex (botany) ,Glucose ,Endocrinology ,Complementary and alternative medicine ,chemistry ,Positron-Emission Tomography ,Antidepressant ,Radiopharmaceuticals ,business ,Research Article ,medicine.drug - Abstract
Background Chronic unpredictable stress (CUS) can cause behavioral and physiological abnormalities that are important to the prediction of symptoms of depression that may be associated with cerebral glucose metabolic abnormalities. Curcumin showed potential antidepressant effects, but whether or not it can reverse cerebral functional abnormalities and so ameliorate depression remains unknown. Methods To investigate the effects of curcumin on brain activity in CUS rats, rats were subjected to 3 weeks of CUS and then treated with curcumin orally at a dose of 40 mg/kg/day for one month. 18 F fluorodeoxyglucose (18 F-FDG)-micro positron emission tomography (micro-PET) neuroimaging was used to detect changes in cerebral metabolism. Body weight, sucrose preference, and open field tests were used to record depressive behaviors during CUS and after curcumin treatment. Results Three weeks of CUS significantly decreased body weight, sucrose preference, sucrose consumption, total distance travelling, and the number of rearing events. It also induced metabolic alterations in several parts of the brain, showing increased glucose metabolism in the right hemisphere. After curcumin treatment for one month, sucrose preference, sucrose consumption, total distance travelling, and the number of rearing events returned to normal levels. Curcumin treatment also induced strong deactivation of the left primary auditory cortex and activation of amygdalohippocampal cortex. Conclusion Curcumin was found to ameliorate the abnormalities in the behavior and brain glucose metabolism caused by CUS, which may account for its antidepressive effects.
- Published
- 2013
37. A direct androgenic involvement in the expression of human corticotropin-releasing hormone
- Author
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Ai-Min Bao, Unga A. Unmehopa, Rawien Balesar, Jiang-Ning Zhou, Wu Yh, Elly M. Hol, Dick F. Swaab, David F. Fischer, Other departments, Other Research, Medical Biology, and Netherlands Institute for Neuroscience (NIN)
- Subjects
Adult ,Male ,medicine.medical_specialty ,endocrine system ,Corticotropin-Releasing Hormone ,medicine.drug_class ,Response Elements ,Cellular and Molecular Neuroscience ,Corticotropin-releasing hormone ,Internal medicine ,medicine ,polycyclic compounds ,Humans ,Testosterone ,Tissue Distribution ,Receptor ,Molecular Biology ,Aged ,Aged, 80 and over ,Mood Disorders ,Chemistry ,Colocalization ,Middle Aged ,Androgen ,Androgen receptor ,Psychiatry and Mental health ,Endocrinology ,nervous system ,Receptors, Androgen ,Hypothalamus ,Female ,hormones, hormone substitutes, and hormone antagonists ,Paraventricular Hypothalamic Nucleus ,Hormone - Abstract
We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.
- Published
- 2006
38. Diurnal rhythm of free estradiol during the menstrual cycle
- Author
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Cao Yx, Liu Ry, Jiang-Ning Zhou, Michel A. Hofman, van Someren Ej, and Ai-Min Bao
- Subjects
Activity Cycles ,Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Luteal phase ,Biology ,Models, Biological ,Endocrinology ,Rhythm ,Diurnal cycle ,Internal medicine ,Follicular phase ,medicine ,Humans ,Circadian rhythm ,Saliva ,Menstrual cycle ,Menstrual Cycle ,Ultradian rhythm ,media_common ,Estradiol ,Diurnal temperature variation ,General Medicine ,Circadian Rhythm ,Female - Abstract
OBJECTIVE: To investigate the diurnal rhythm of estrogens in normally cyclic women during reproductive life. DESIGN: Multiple saliva sampling in normally cyclic healthy women during reproductive life at different phases of their menstrual cycles was carried out. METHODS: Salivary estradiol was measured by radioimmunoassay in samples collected every 2 h for 24 h from 15 normally cyclic healthy women during reproductive life during the menstrual phase, the late follicular/peri-ovulation phase, the early to mid luteal phase and the late luteal phase, respectively, of their menstrual cycles. The levels of salivary estradiol were analyzed by means of periodic regression. RESULTS: A daily biological rhythm of free estradiol was found after quantification with a nonlinear periodic regression model. The observed diurnal free estradiol rhythm consists of two major components: an asymmetrically peaked diurnal cycle and ultradian harmonics in the range of 6 to 12 h. The diurnal and ultradian rhythms were remarkably consistent throughout the menstrual cycle in terms of mesor (24 h mean level), peak width and amplitude. There was a tendency for the 24-h rhythm acrophases to converge in the early morning, while the acrophase of the menstrual phase occurred significantly later than in the late follicular/peri-ovulation phase. CONCLUSIONS: The diurnal rhythm of estradiol has a similar complex temporal organization for different menstrual phases. The menstrual cycle mainly modulates the acrophase of the diurnal rhythm.
- Published
- 2003
39. MicroRNA-132 and early growth response-1 in nucleus basalis of Meynert during the course of Alzheimer's disease.
- Author
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Qiong-Bin Zhu, Unmehopa, Unga, Bossers, Koen, Yu-Ting Hu, Verwer, Ronald, Balesar, Rawien, Juan Zhao, Ai-Min Bao, Swaab, Dick, Zhu, Qiong-Bin, Hu, Yu-Ting, Zhao, Juan, and Bao, Ai-Min
- Subjects
ALZHEIMER'S disease treatment ,NEURODEGENERATION ,MICRORNA ,CELL growth ,CHOLINERGIC mechanisms ,NEURAL physiology - Abstract
The cholinergic nucleus basalis of Meynert, which is important for memory functions, shows neuronal activation ('up-phase') during the early stages of Alzheimer's disease and neurodegeneration ('down-phase') in later stages of Alzheimer's disease. MicroRNA-132 (miR-132) and the transcription factor early growth response-1 (EGR1) were proposed as possible candidate molecules regulating such an up-down activity pattern of the nucleus basalis of Meynert during the course of Alzheimer's disease, as they both show this up-down pattern of expression in the prefrontal cortex during the course of Alzheimer's disease. Not only do these two molecules stimulate synaptic activity and plasticity, they are also involved in Alzheimer's disease pathology and might, in addition, affect cholinergic function. In the nucleus basalis of Meynert, we investigated the expression of miR-132 and EGR1 along the entire course of Alzheimer's disease. Forty-nine post-mortem nucleus basalis of Meynert samples were studied, ranging from non-demented controls (Braak stage = 0) to late Alzheimer's disease patients (Braak stage = VI), and from clinical Reisberg scale 1 to 7. Each Braak stage contained seven samples, that were all well matched for confounding factors, i.e. age (range 58-91), sex, post-mortem delay, cerebrospinal fluid pH (as a measure for agonal state), APOE genotype, clock time of death, tissue fixation time, and tissue storage time. The alterations of these two molecules were studied over the course of Alzheimer's disease in relation to the expression of 4G8-stained amyloid-β, hyperphosphorylated tau stained by antibody AT8, neuronal fibrillary tangles and neuropil threads stained by silver, and in relation to alterations in choline acetyltransferase. We found that the expression of miR-132 and EGR1 in the nucleus basalis of Meynert was quite stable during the early stages of Alzheimer's disease and decreased significantly only during late Alzheimer's disease stages. In addition, miR-132 and EGR1 showed a significant positive correlation with choline acetyltransferase expression (r = 0.49, P < 0.001 and r = 0.61, P < 0.001), while choline acetyltransferase expression showed a significantly negative correlation with hyperphosphorylated tau (r = -0.33, P = 0.021) but no correlation with 4G8-stained amyloid-β. From the functional changes of miR-132 and EGR1 along the course of Alzheimer's disease we conclude: (i) that these two molecules may play a role in keeping the cholinergic function intact in early Alzheimer's disease stages; and (ii) that these molecules may contribute to the late neurodegeneration of this cholinergic nucleus. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
40. Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.
- Author
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Yun-Rong Lu, Xin-Yan Fu, Li-Gen Shi, Yan Jiang, Juan-Li Wu, Xiao-Juan Weng, Zhao-Pin Wang, Xue-Yan Wu, Zheng Lin, Wei-Bo Liu, Hui-Chun Li, Jian-Hong Luo, and Ai-Min Bao
- Subjects
BLOOD plasma ,AMINO acids in the blood ,NEUROTRANSMITTERS ,MENTAL depression ,NITRIC oxide ,GABA ,CEREBROSPINAL fluid - Abstract
Background Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder. Methods Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects. Results The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds. Conclusion These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
41. Colocalization of corticotropin-releasing hormone and oestrogen receptor-α in the paraventricular nucleus of the hypothalamus in mood disorders.
- Author
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Ai-Min Bao, Andon Hestiantoro, Eus J. W. Van Someren, Dick F. Swaab, and Jiang-Ning Zhou
- Published
- 2005
- Full Text
- View/download PDF
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