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Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists. [ABSTRACT FROM AUTHOR]

Background: Stroke has always been a major threat worldwide but is most severe in China, with 2.5 million new stroke cases each year and 7.5 million stroke survivors, placing a heavy burden on the social and national health care systems. Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine (TCM) that has been used clinically for many years in China. To explore the potential mechanism of ZRS in the treatment of stroke, liquid chromatography with mass spectrometry (LC–MS) was performed. Methods: In this study, a quantitative proteomic method with LC–MS was used to analyse the proteomic differences between MACO samples treated with ZRS and those without ZRS treatment. Results: Liquid chromatography with mass spectrometry (LC–MS) analysis led to the identification of 35,006 peptides, with 5160.0 proteins identified and 4094.0 quantified. Significantly differentially expressed proteins were identified through data analysis, and the difference was found to be more than 1.2 times (P < 0.05). The Gene Ontology (GO) analysis provided a summary of the dysregulated protein expression in the biological process (BP), cell component (CC), and molecular function (MF) categories. Proteins related to brain repair, including BDNF, IL-10, IL-6, and TGF-β, were found to change significantly, partially demonstrating the effectiveness of ZRS to attenuate tissue injury. Conclusion: In this study, LC–MS/MS was performed to assess the effects of ZRS on differentially expressed proteins in rats with cerebral infarction. These promising results could help to improve the understanding of the effects of drugs on stroke. [ABSTRACT FROM AUTHOR]

As a commercially important species, the Chinese mitten crab (Eriocheir sinensis) has been cultured for a long time in China. Agonistic behavior often causes limb disability and requires much energy, which is harmful to the growth and survival of crabs. In this paper, we divided crabs into a control group (control, no treatment) and an experimental group (fight, agonistic behavior after 1 h) and then collected the thoracic ganglia (TG) to extract RNA. Subsequently, we first used a deep sequencing approach to examine the transcripts of microRNAs (miRNAs) and messenger RNAs (mRNAs) in E. sinensis displaying agonistic behavior. According to the results, we found 29 significant differentially expressed miRNAs (DEMs) and 116 significant differentially expressed unigenes (DEGs). The DEMs esi-miR-199a-5p, esi-let-7d, esi-miR-200a, and esi-miR-200b might participate in the regulation of agonistic behavior by mediating neuroregulation and energy metabolism. Focusing on the transcripts of the mRNAs, the renin–angiotensin system (RAS) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway might be involved in the regulation of agonistic behavior through glucose metabolism as this pathway was significantly enriched with DEGs. Besides, an integrated analysis of the miRNA and mRNA profiles revealed that the retinoid X receptor (RXR) was also involved in visual signal transduction, which was important for agonistic behavior. In addition, four vital agonistic behavior-related metabolic pathways, including the cAMP signaling, MAPK, protein digestion and absorption, and fatty acid metabolism pathways, were significantly enriched with the predicted target unigenes. In conclusion, the findings of this study might provide important insight enhancing our understanding of the underlying molecular mechanisms of agonistic behavior in E. sinensis. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. Huatuo Zaizao pill (HT), a traditional Chinese medicine, has been used clinically in China to promote the rehabilitation after stroke, but the underlying mechanism of action was still unclear. This study is to investigate the effects of HT on the functional recovery in a rat model of cerebral ischemia-reperfusion (I/R) injury, and the potential molecular mechanisms. Methods: Rats were randomly divided into sham, model with cerebral I/R injury, or HT-treated groups, then administered orally with vehicle (for the sham and model group) or HT (0.5, 1.0, or 2.0 mg/kg) respectively, for 3 or 7 days. Functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Neurogenesis was investigated by double immunofluorescence staining for 5-ethynyl-2-deoxyuridine (EdU) and neuronal nuclear protein (NeuN). The proteins of kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were assayed by western blotting. The level of BDNF mRNA was evaluated by RT-PCR. Results: Compared with the model group, treatment with HT significantly promoted functional recovery in I/R injured rats (p < 0.05 or p < 0.01). The generation of new neurons was increased in the HT groups. HT treatment for 3 days increased the level of BDNF mRNA in I/R injured rats. Expression of PKA, phosphorylated CREB, and BDNF were significantly (p < 0.05) increased with the 7-day HT treatment. Conclusions: These results indicated that HT treatment could promote functional recovery after stroke. HT enhanced the expression of BDNF and increased the level of neurogenesis in cerebral I/R animal, which might be associated with the functional recovery. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance An efficacious antidepressant without unwanted side effects is need urgently at present. This study aimed to investigate whether treatment with four Chinese herbal medicines (CHMs), namely Radix Astragali, S aposhnikovia divaricate (SD), Eucommia ulmoides Oliv. bark (EU), and Corydalis yanhusuo W. T. Wang ( C. yanhusuo ), could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model and the potential mechanism(s) of their action. Materials and methods In vitro study, the proliferation of NSCs was assessed using the MTS assay. In vivo study, chronic mild stress (CMS) was used in mice for 14 days to establish a depression-like mouse model. Plasma corticosterone levels were assessed by UPLC coupled to a triple-quadrupole mass spectrometer. The forced swim test (FST) was used to assess the effects of the four CHMs on depression. BrdU incorporation and TUNEL staining were used to assay hippocampal precursor cell proliferation rate and apoptosis. Results The CHMs included Radix Astragali , EU, C. yanhusuo , and SD were shown to promote neuroproliferation in vitro . In vivo study, oral administration of these four CHMs for 14 days reversed the elevated plasma corticosterone levels, body weight loss, decrease in proliferation of hippocampal precursor cells; they also inhibited hippocampal cell apoptosis, and exhibited an antidepressant-like effect in a depression-like mouse model induced by CMS. Conclusions Our study indicates that each of these CHMs has the potential to ameliorate depression. The possible mechanisms of action include modulation of the HPA axis, reduction in stress hormone levels, inhibition of apoptosis, and promotion of hippocampal neuronal plasticity and neurogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Tongxinluo, a well-known traditional Chinese medicine complex, has been widely used for the treatment of cerebrovascular diseases in China. The present study was to explore whether treatment with tongxinluo could improve neurological function and alleviate secondary damage in the ipsilateral thalamus after focal cortical infarction in hypertensive rats. Methods: Tongxinluo was given through oral gavage starting 24 h after distal middle cerebral artery occlusion (MCAO). Neurological function was assessed and then rats were sacrificed 7 and 14 days after MCAO. Brains were harvested for examining infarction volume, Nissl staining and immunofluorescence analysis. Results: Compared with vehicle treatment, tongxinluo remarkably improved neurological function without reducing infarction volume, attenuated neuronal loss and astrocyte activation in the ipsilateral thalamus 7 and 14 days after MCAO (all p < 0.05). Also, tongxinluo markedly increased the number of BrdU+/nestin+ and BrdU+/NeuN+ cells 14 days after MCAO. Moreover, vascular density, the number of BrdU+ vascular endothelial cells, and vascular perimeter in the ipsilateral thalamus were markedly increased in the tongxinluo group relative to that of the vehicle group (all p < 0.05). Conclusion: Administration of tongxinluo 24 h after cortical infarction may promote neurogenesis and angiogenesis in the ipsilateral thalamus and improves neurological function after cortical infarction in rats. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease caused by aging, environmental and genetic factors, and many susceptibility genes have been found to increase the risk for PD. Lin28a, an RNA binding protein, is expressed prominently in neural progenitor cells. The expression of Lin28a is decreased gradually with neural differentiation and is implicated in oncogenesis, glucose metabolism, neurogenesis, and neurogliogenesis. However, few genetic studies have explored the association between rare variants of the LIN28A gene and PD yet. Our study recruited 3,879 PD patients and 2,931 controls, and they were divided into two cohorts, including the EOPD & FPD cohort and the LOPD cohort, separately sequenced by whole-exome sequencing and whole-genome sequencing. We found nine rare nonsynonymous variants in the coding region of the LIN28A gene, but the rare variants of this gene were not enriched in PD patients in both cohorts. Thence, our study did not support the association between the LIN28A gene and the PD risk in the Chinese mainland population., (Copyright © 2022. Published by Elsevier B.V.)

Abstract: Ethnopharmacological relevance: Ginseng, the root of Panax ginseng C.A. Meyer, is one of the most commonly used healing herbs for stroke and chronic debilitating conditions in China. Ginsenosides are the main active principles for ginseng''s efficacy, but the mechanisms have not been fully clarified. Aim of the study: To test the hypothesis whether or not the administration of Ginseng total saponins (GTS) can enhance neurogenesis after focal cerebral ischemia, and thereby improve neurological deficits. Materials and methods: Male Wistar rats received intraperitoneal injections of GTS dissolved at a dose of 25mgkg−1 d−1 or normal saline (NS) of same volume 3 days before the permanent middle cerebral artery occlusion (MCAO) model establishment until the animals were killed at the time points of 1d, 3d, 7d and 14d. The neurological function was assessed blindly. BrdU immunostaining and double staining were performed by following the 3-steps method. Results: (A) GTS-treated rats have better neurological scores compared with those in NS group at 14d time point (p <0.05); (B) the number of BrdU+ cells and BrdU+/NeuN+ cells in GTS group were significantly higher than those in NS group in the ipsilateral subventricular zone and in the ipsilateral infarct area after MCAO, respectively (p <0.05 or p <0.01); (C) the increase of the number of BrdU+/NeuN+ cells highly correlated with the decrease of neurological scores. Coefficient correlation r =−0.828 (p <0.01). Conclusion: GTS can improve neurological deficits after focal cerebral ischemia by inducing endogenous neural stem cells activation and thereby enhance adult central nervous system regeneration. [Copyright &y& Elsevier]

Aim of the study: Recent studies have revealed that ginsenoside Rb1 (GRb1) is neuroprotective for cerebral ischemia. However, the mechanism underlying of this function is unclear. We assessed whether this neuroprotective effect of GRb1 was mediated by the levels of brain-derived neurotrophic factor (BDNF), by the levels of caspase-3 proteins and by induced neurogenesis in rats following transient cerebral ischemia or not. Materials and methods: Cerebral ischemia was prepared by a 2h occlusion of the middle cerebral artery and reperfusion, followed by infusion of GRb1 (40mg/kg) and saline (GRb1 and ischemia groups, respectively). All rats were sacrificed at 3 and 12h, 1, 2, 3, 5, and 10 days after reperfusion. Normal and sham-operated rats were used in control group. Modified Neurological Severity Scores (mNSS) test and hematoxylin and eosin staining were respectively performed to evaluate neurological function and histological feature. Immunohistochemistry was used to identify intrinsic neurogenesis by nestin antibody. Western blotting was used to detect BDNF and caspase-3 protein content. Results: GRb1 infusion after cerebral ischemia significantly promoted recoveries of neurological functions at 3 and 5 days after reperfusion compared to ischemic rats. The number of nestin-positive cells was apparently increased after GRb1 infusion compared to ischemia rats at given time. Moreover, BDNF was significantly increased in GRb1-treated rats compared to ischemia rats at different time points. In contrast, GRb1 infusion after the onset of reperfusion, caspase-3 at a given time was significantly reduced compared to ischemia rats, but still significantly increased compared to control rats. Conclusions: Promotion of the neurogenesis and regulation of the expressions of BDNF and caspase-3 may be involved in GRb1-induced neuroprotection against cerebral ischemia. [Copyright &y& Elsevier]

Background: Neural stem cell treatment and neurogenesis stimulation have gained attention as potential treatments for vascular dementia (VD). Currently, research mainly focuses on neurogenesis occurring in the sub-ventricular zone and dentate gyrus, while the research of the piriform cortex (Pir) is limited. Few results showed that weak neurogenesis exists in the Pir of adult rats. Since neurogenesis occurs in the Pir and is closely related to cognitive function, this study addressed the question of whether neurogenesis occurs in the Pir of an animal with the VD. Primary objective and hypothesis: This study investigated the effects of hyperbaric oxygen therapy on brain blood supply and neurogenesis in the piriform cortex (Pir) of rats with VD. Main outcomes and results: Compared to non-VD control rats (NC), rats with VD showed reduced rCBF, increased rCBV and slower MTT in the Pir. However, following hyperbaric oxygen (HBO) treatment in VD rats, rCBF increased, rCBV decreased and MTT increased. To determine whether the restoration in brain blood supply was associated with increased neurogenesis, immunohistochemical detection of nestin and doublecortin (DCX) was used. In the Pir of both normal and VD rats, nestin positive cells were localized to layer II (superficial cellular layer) and layer III (deep cellular layer). Nestin expression was increased in Pir cells in VD rats and was even more intensely expressed after the HBO treatment. DCX positive cells were mostly located in layer II from amygdaline fissure to rhinal fissure. Conclusion: These results suggest that HBO therapy can improve the blood supply and promote the neurogenesis in the Pir of adult rats with the VD. [ABSTRACT FROM AUTHOR]

Stroke is one of the main causes of disease-related mortality worldwide. Buyang Huanwu Decoction (BHD) has been used to protect against stroke and stroke-induced disability for several years in China. Studies have shown that BHD can relieve neuronal damage in rats with cerebral ischemia/reperfusion (I/R) injury. However, the mechanism remains unclear. A middle cerebral artery occlusion and reperfusion (MCAO-R) model was used in the present study. The animals were treated with BHD (5, 10 and 20 g/kg) or rapamycin. Infarct size and modified neurological severity score were calculated on day 5 following MCAO-R surgery. Cellular changes around the ischemic penumbra were revealed by hematoxylin and eosin and Nissl staining. The protein expression levels of nestin, brain-derived neurotrophic factor (BDNF), doublecortin on the X chromosome (DCX) and autophagy-related proteins (beclin 1, LC3-II and p62) in the peri-ischemic area of the brain were detected. The results demonstrated that post-surgical treatment with BHD reduced the brain infarct size and improved neurological deficits in MCAO-R rats. BHD protected against MCAO-R-induced neuronal impairment and promoted neurogenesis, increased the protein expression of nestin, BDNF and DCX and markedly enhanced autophagy by increasing beclin 1 and LC3-II and decreasing p62. Meanwhile, BHD promoted the expression of sirtuin 1 (SIRT1), an important regulator of autophagy. In conclusion, the present study suggested that post-surgical treatment with BHD could protect rat brains from I/R injury, potentially through the SIRT1/autophagy pathway. [ABSTRACT FROM AUTHOR]

At present, Stroke is still one of the leading causes of population death worldwide and leads to disability. Traditional Chinese medicine plays an important role in the prevention or treatment of stroke. l -borneol, a traditional Chinese medicine, has been used in China to treat stroke for thousands of years. However, its mechanism of action is unclear. After cerebral ischemia, promoting angiogenesis after cerebral ischemia and providing nutrition for the infarct area is an important strategy to improve the damage in the ischemic area, but it is also essential to promote neurogenesis and replenish new neurons. Here, our research shows that l -borneol can significantly improve the neurological deficits of pMCAO model rats, reduce cerebral infarction, and improve the pathological damage of cerebral ischemia. and significantly increase serum level of Ang-1 and VEGF, and significantly decrease level of ACE and Tie2 to promote angiogenesis. PCR and WB showed the same results. Immunohistochemistry also showed that l- borneol can increase the number of CD34 positive cells, further verifying that l- borneol can play a neuroprotective effect by promoting angiogenesis after cerebral ischemia injury. In addition, l- borneol can significantly promote the expression level of VEGF, BDNF and inhibit the expression levels of TGF-β1 and MMP9 to promote neurogenesis. The above suggests that l- borneol can promote angiogenesis coupled neurogenesis by regulating Ang1-VEGF-BDNF to play a neuroprotective effect. Molecular docking also shows that l- borneol has a very high binding rate with the above target, which further confirmed the target of l- borneol to improve cerebral ischemic injury. These results provide strong evidence for the treatment of cerebral ischemia with l- borneol and provide reference for future research. [ABSTRACT FROM AUTHOR]

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha ( kucha ), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis . This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.

Objectives: To investigate whether curcumin promotes hippocampal neurogenesis in the cerebral ischemia (CI) mice via Wnt/β-catenin signaling pathway., Methods: Male C57BL/6 mice were randomly divided into groups: sham operation group (Sham), cerebral ischemic group (CI), curcumin treatment group (50, 100 mg/kg/d, i.p.) and curcumin (100 mg/kg/d) + DKK1 (a blocker of Wnt receptor, 200 ng/d, icv) group. CI was induced by bilateral common carotid arteries occlusion (BCCAO) for 20 min. The Morris water maze test was conducted to detect spatial learning and memory. Immunofluorescence staining was used to examine the proliferation and differentiation of immature neurons in the hippocampal dentate gyrus. The proteins involved in neurogenesis and Wnt signaling pathway were examined using Western blot assay., Results: Curcumin significantly alleviated cognitive deficits induced by CI. Curcumin dose-dependently increased the proliferation of neural stem cells and promoted the differentiation and maturation of newly generated neural cells into neurons. Curcumin also increased the expression of proteins involved in neurogenesis (including Ngn2, Pax6 and NeuroD 1) and the Wnt/β-catenin signaling pathway. Moreover, the forenamed effects of curcumin were abolished by pretreatment with DKK1, a blocker of Wnt receptor., Conclusion: Curcumin promotes hippocampal neurogenesis by activating Wnt/β-catenin signaling pathway to ameliorate cognitive deficits after acute CI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Backgrounds: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC., Methods: In this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency., Results: The protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker., Conclusion: Taken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Neural stem cells (NSCs) are one specific type of multipotential stem cells that have the ability to proliferate for a long time and to differentiate into neural cells, including neurons, astrocytes and oligodendrocytes. These NSCs exist in both the embryonic and adult central nervous system (CNS) of all mammalian species. Progress has been made in the understanding of the developmental regulation of NSCs and their function in neurogenesis. This review discusses recent progress in this area, with emphasis on work done by investigators in China.

Synapses are specialized structures that mediate information flow between neurons and target cells, and thus are the basis for neuronal system to execute various functions, including learning and memory. There are around 10(11) neurons in the human brain, with each neuron receiving thousands of synaptic inputs, either excitatory or inhibitory. A synapse is an asymmetric structure that is composed of pre-synaptic axon terminals, synaptic cleft, and postsynaptic compartments. Synapse formation involves a number of cell adhesion molecules, extracellular factors, and intracellular signaling or structural proteins. After the establishment of synaptic connections, synapses undergo structural or functional changes, known as synaptic plasticity which is believed to be regulated by neuronal activity and a variety of secreted factors. This review summarizes recent progress in the field of synapse development, with particular emphasis on the work carried out in China during the past 10 years (1999-2009).