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Blue gourami (gourami, Trichogaster trichopterus) is a model for labyrinth fishes (Anabantoidei) adapted to partial air breathing. Its reproductive endocrinology has been extensively studied, and transcriptomic sex differences in the gonads were described. Nevertheless, sex differences in gene expression in non-gonadal tissues ostensibly affected by the sex-specific hormonal balance, e.g., the brain, are unknown. To assess such differences, we used bulk RNA-seq to assemble and compare polyA+ transcriptomes between whole brains of four adult male and five adult female gourami, in addition to other tissues (three dorsal fin and five ovary samples) from the same female group. While all nine brain transcriptomes clustered together relative to the other tissues, they showed separation according to sex. A total of 3568 genes were differentially expressed between male and female brains; of these, 1962 and 1606 showed lower and higher expression in males, respectively. Male brains showed stronger down-regulation of specific genes, which included hormone receptors, e.g., pituitary adenylate cyclase-activating polypeptide receptor (pacap-r1). Among the genes with lower expression in male brains, multiple pathways essential to brain function were over-represented, including GABA, acetylcholine and glutamate receptor signaling, calcium and potassium transmembrane transport, and neurogenesis. In contrast, genes with higher expression in male brains showed no significant over-representation of brain-specific functions. To measure the mRNA levels of specific hormone receptors known from prior studies to regulate reproductive function and behavior in gourami and to validate RNA-seq results for these specific genes, we performed RT-qPCR for five receptors, pacap-r1, gonadotropin-releasing hormone 2 receptor (gnrh2r), kisspeptin receptor 1 (gpαr1/kiss1), insulin-like growth factor 1 receptor (igf1r), and membrane progesterone receptor 1 (mpr1), in the brain RNA sample groups. Of these, pacap-r1 showed a significant, three-fold down-regulation, while gpαr1/kiss1 showed a significant two-fold down-regulation in male vs. female gourami brains. Our results are novel in describing the suppression of brain function-related gene expression in male, as compared to female, gourami brains. Further research is needed to assess the behavioral significance of this effect and its prevalence in other vertebrate groups. [ABSTRACT FROM AUTHOR]

Objective To analyze the effects of mild hypothermia assisted minimally invasive puncture and drainage on the levels of matrix metalloproteinase-9 (MMP-9), neuron-specific enolase (NSE), central nervous specific protein ($1008) and neurological function in patients with acute cerebral hemorrhage. Methods A total of 108 patients with acute cerebral hemorrhage admitted to our hospital from January 2021 to January 2023 were selected and divided into the experimental group and the control group by random number table method. with 54 cases in each group. The experimental group was treated with mild hypothermia assisted minimally invasive puncture and drainage and the control group was treated with minimally invasive puncture and drainage at each time point(immediately after operation. 3 and 7 days after operation), brain tissue damage. serum retinol binding protein 4(RBP4) granulocyte macrophage colony stimulating factor(GM- CSF), human cartilage glycoprotein 39 (YKL-40) levels before operation and 7 days after operation, neurological function and complications during hospitalization were compared between the two groups. Results Compared with immediately after operation, the intracranial pressure of the two groups increased significantly at 3 and 7 days after operation. Compared with 3 days after operation, the intracranial pressure of the two groups decreased significantly at 7 days after operation. The intracranial pressure of the study group was significantly lower than that of the control group at 3 and 7 days after operation. and the differences were statistically significant (P<0,05). Compared with before operation, the levels of serum NSE, S1003. MMP-9, RBP4.GM-CSF and YKL-40 in the two groups were significantly decreased on the 7th day after operation and the levels of serum NSE. S100ß, MMP-9, RBP4, GM-CSF and YKL-40 in the study group were significantly lower than those in the control group on the 7th day after operation, the differences were statistically significant(P< 0.05). The Glasgow coma scores of the two groups were significantly increased at 7 days after operation. and the Glasgow coma scores of the study group were significantly higher than those in the control group at 7 days after operation, with statistical significance (P<0.05). Compared with the preoperative results. the scores of National Institutes of Health Stroke Scale in the two groups were significantly decreased at 6 months after operation and the scores of European Stroke Scale were significantly increased. The scores of National Institutes of Health Stroke Scale in the study group were significantly lower than those in the control group at 6 months after operation and the scores of European Stroke Scale were significantly higher than those in the control group, with statistical significance (P<0.05). There was no significant difference being found in the comparison of the incidence of complications during hospitalization between the two groups (P>0.05). Conclusion Mild hypothermia assisted minimally invasive puncture and drainage could reduce intracranial pressure in patients with acute cerebral hemorrhage regulate the levels of MMP-9. NSE. $100ß, reduce brain tissue damage. regulate the expression of RBP4.GM-CSF.YKL-40.and ultimately improve the effect of neuro- logical function with good safety. [ABSTRACT FROM AUTHOR]

Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Blue gourami (gourami, Trichogaster trichopterus) is a model for labyrinth fishes (Anabantoidei) adapted to partial air breathing. Its reproductive endocrinology has been extensively studied, and transcriptomic sex differences in the gonads were described. Nevertheless, sex differences in gene expression in non-gonadal tissues ostensibly affected by the sex-specific hormonal balance, e.g., the brain, are unknown. To assess such differences, we used bulk RNA-seq to assemble and compare polyA+ transcriptomes between whole brains of four adult male and five adult female gourami, in addition to other tissues (three dorsal fin and five ovary samples) from the same female group. While all nine brain transcriptomes clustered together relative to the other tissues, they showed separation according to sex. A total of 3568 genes were differentially expressed between male and female brains; of these, 1962 and 1606 showed lower and higher expression in males, respectively. Male brains showed stronger down-regulation of specific genes, which included hormone receptors, e.g., pituitary adenylate cyclase-activating polypeptide receptor (pacap-r1). Among the genes with lower expression in male brains, multiple pathways essential to brain function were over-represented, including GABA, acetylcholine and glutamate receptor signaling, calcium and potassium transmembrane transport, and neurogenesis. In contrast, genes with higher expression in male brains showed no significant over-representation of brain-specific functions. To measure the mRNA levels of specific hormone receptors known from prior studies to regulate reproductive function and behavior in gourami and to validate RNA-seq results for these specific genes, we performed RT-qPCR for five receptors, pacap-r1, gonadotropin-releasing hormone 2 receptor (gnrh2r), kisspeptin receptor 1 (gpαr1/kiss1), insulin-like growth factor 1 receptor (igf1r), and membrane progesterone receptor 1 (mpr1), in the brain RNA sample groups. Of these, pacap-r1 showed a significant, three-fold down-regulation, while gpαr1/kiss1 showed a significant two-fold down-regulation in male vs. female gourami brains. Our results are novel in describing the suppression of brain function-related gene expression in male, as compared to female, gourami brains. Further research is needed to assess the behavioral significance of this effect and its prevalence in other vertebrate groups.

Abstract Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research.

Accumulating evidence has suggested that prenatal exposure to methadone causes multiple adverse effects on human brain development. Methadone not only suppresses fetal neurobehavior and alters neural maturation, but also leads to long-term neurological impairment. Due to logistical and ethical issues of accessing human fetal tissue, the effect of methadone on brain development and its underlying mechanisms have not been investigated adequately and are therefore not fully understood. Here, we use human cortical organoids which resemble fetal brain development to examine the effect of methadone on neuronal function and maturation during early development. During development, cortical organoids that are exposed to clinically relevant concentrations of methadone exhibited suppressed maturation of neuronal function. For example, organoids developed from 12th week till 24th week have an about 7-fold increase in AP firing frequency, but only half and a third of this increase was found in organoids exposed to 1 and 10 μM methadone, respectively. We further demonstrated substantial increases in I Na (4.5-fold) and I KD (10.8-fold), and continued shifts of Na+ channel activation and inactivation during normal organoid development. Methadone-induced suppression of neuronal function was attributed to the attenuated increase in the densities of I Na and I KD and the reduced shift of Na+ channel gating properties. Since normal neuronal electrophysiology and ion channel function are critical for regulating brain development, we believe that the effect of prolonged methadone exposure contributes to the delayed maturation, development fetal brain and potentially for longer term neurologic deficits.

Advanced age is typically associated with a decrease in cognitive function including impairment in the formation and retention of new memories. The hippocampus is critical for learning and memory, especially spatial learning, and is particularly affected by ageing. With advanced age, multiple neural components can be detrimentally affected including a reduction in the number of neural stem and precursor cells, a decrease in the formation of adult born neurons (neurogenesis), and deficits in neural circuitry, all of which ultimately contribute to impaired cognitive function. Importantly, physical exercise has been shown to ameliorate many of these impairments and is able to improve learning and memory. Relevantly, growth hormone (GH) is an important protein hormone that decreases with ageing and increases following physical exercise. Originally described due to its role in longitudinal growth, GH has now been identified to play several additional key roles, especially in relation to the brain. Indeed, the regular decrease in GH levels following puberty is one of the most well documented components of neuroendocrine ageing. Growth hormone deficiency (GHD) has been described to have adverse effects on brain function, which can be ameliorated via GH replacement therapy. Physical exercise has been shown to increase circulating GH levels. Furthermore, we recently demonstrated the increase in exercise-mediated GH is critical for improved cognitive function in the aged mouse. Here we examine the multiple roles that GH plays, particularly in the aged brain and following trauma, irradiation and stroke, and how increasing GH levels can ameliorate deficits in cognition. [ABSTRACT FROM AUTHOR]

Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research. [ABSTRACT FROM AUTHOR]

Advanced age is typically associated with a decrease in cognitive function including impairment in the formation and retention of new memories. The hippocampus is critical for learning and memory, especially spatial learning, and is particularly affected by ageing. With advanced age, multiple neural components can be detrimentally affected including a reduction in the number of neural stem and precursor cells, a decrease in the formation of adult born neurons (neurogenesis), and deficits in neural circuitry, all of which ultimately contribute to impaired cognitive function. Importantly, physical exercise has been shown to ameliorate many of these impairments and is able to improve learning and memory. Relevantly, growth hormone (GH) is an important protein hormone that decreases with ageing and increases following physical exercise. Originally described due to its role in longitudinal growth, GH has now been identified to play several additional key roles, especially in relation to the brain. Indeed, the regular decrease in GH levels following puberty is one of the most well documented components of neuroendocrine ageing. Growth hormone deficiency (GHD) has been described to have adverse effects on brain function, which can be ameliorated via GH replacement therapy. Physical exercise has been shown to increase circulating GH levels. Furthermore, we recently demonstrated the increase in exercise-mediated GH is critical for improved cognitive function in the aged mouse. Here we examine the multiple roles that GH plays, particularly in the aged brain and following trauma, irradiation and stroke, and how increasing GH levels can ameliorate deficits in cognition.

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Purpose: To investigate the neuroprotective effects of deloratine A on liposaccharide (LPS)-induced microglia activation in vitro and in a rat model of ischemia-reperfusion injury. Methods: LPS-induced microglial activation was successfully established in mouse microglia BV2 cell line. Then, the cells were randomly divided into model group, 2.5 μM delavatine A group, 5 μM delavatine A group, and 10 μM delavatine A group. The effect of delavatine A on the release of NO, TNF-α, IL-1β and IL-6 in BV2 cells was determined. In the vivo studies, 21 male Sprague Dawley (SD) rats were used to establish a rat model of ischemia-reperfusion injury, and effect of delavatine A on neural function and cerebral infarction area was determined. Results: The NO content was significantly higher in LPS-induced microglial activation model than in blank control, but it was significantly lower in the 3 delavatine A groups than in model group (p < 0.05). The expression levels of TNF-α, IL-1β, and IL-6 were significantly higher in model group than in blank control group, but they were significantly and dose-dependently lower in delavatine A groups than in model group (p < 0.05). In the in vivo rat studies, neural function score and cerebral infarction area in the model group were significantly higher than those in the sham group, while cerebral infarction area in delavatine A groups were significantly lower than that in the model group (p < 0.05). Conclusion: Delavatine A significantly reduces the inflammation associated with LPS-induced microglial activation, mitigates loss of neural function, and reduces cerebral infarction area in rats with ischemia-reperfusion injury. These findings may lead to the development of new neuroprotective drugs. [ABSTRACT FROM AUTHOR]

Cognitive decline is inevitable with age, and due to the lack of well-established pharmacotherapies for neurodegenerative disorders, dietary supplements have become important alternatives to ameliorate brain deterioration. Hydrolyzed chicken meat extract (HCE) and its bioactive components were previously found to improve neuroinflammation and cognitive decline by regulating microglia polarization. However, the effects and mechanisms of these bioactives on neurons remain unclear. Here, the most potent bioactive component on neural function in HCE was screened out, and the detailed mechanism was clarified through in vivo and in vitro experiments. We found that HCE, cyclo(Val-Pro), cyclo(Phe-Phe), cyclo(His-Pro), cyclo(Leu-Lys), and arginine exerted stronger anti-inflammatory and antioxidant effects among the 12 bioactives in amyloid β (Aβ)-treated HT-22 cells. Further transcriptome sequencing and polymerase chain reaction (PCR) array analysis showed that these bioactives participated in different signaling pathways, and cyclo(Val-Pro) was identified as the most potent cyclic dipeptide. In addition, the antiapoptotic and neuroprotective effect of cyclo(Val-Pro) was partly regulated by the activation of PI3K/AKT and AMPK pathways, and the inhibition of these pathways abolished the effect of cyclo(Val-Pro). Moreover, cyclo(Val-Pro) enhanced cognitive function and neurogenesis and alleviated neuroinflammation and oxidative stress in middle-aged mice, with an effect similar to HCE. Hippocampal transcriptome analysis further revealed that HCE and cyclo(Val-Pro) significantly enriched the neuroactive ligand-receptor interaction pathway, verified by enhanced neurotransmitter levels and upregulated neurotransmitter receptor-related gene expression. Therefore, the mechanism of cyclo(Val-Pro) on neural function might be associated with PI3K/AKT and AMPK pathway-mediated antiapoptotic effect and neurogenesis and the activation of the neurotransmitter-receptor pathway.

This experiment determined the duration that rapid heat stress (RHS) impacts neural function and reaction time. Previous research has discovered that RHS results in neural function changes immediately post-exposure. No studies have evaluated the duration that these variables are impacted. Additionally, research has not assessed the impact of RHS on reaction time. We hypothesized that RHS would lead to sustained electroencephalography (EEG) spectral power and reaction time changes. Twenty participants performed a treadmill protocol in an environmental chamber (35 °C; 45% humidity) in firefighter personal protective equipment until reaching a core temperature of 39 °C. The subjects performed a Go/No-Go (response inhibition) task (pre-, post-, 24, and 48 h post-RHS) while EEG and reaction time were recorded. Results from the Go/No-Go task revealed a difference between pre-RHS and post-RHS delta spectral power. These differences support previous literature. The first novel finding of this study is that delta power is still perturbed 24 h post-RHS exposure. The second novel finding is that reaction time is altered post-RHS, 24 h, and 48 h post-RHS. These cognitive changes could result in compounded consequences if two bouts of RHS occur in 24 h (e.g., two fires or other hyperthermic events), which could jeopardize critical life-saving missions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of different doses of phenobarbital sodium on the recovery of neurological function and cognitive impairment in rats with ischemic brain injury. Methods: The rats with ischemic brain injury(n=48) were randomly equally divided into three groups-model group, low-dose group and high-dose group. From the 7th day after modeling, the model group, low-dose group and high-dose group were given intraperitoneal injection of normal saline, phenobarbital sodium 50 mg/kg/d and phenobarbital sodium 100 mg/kg/d, for 7 days, observed and recorded the recovery of neurological function and cognitive impairment in rats. Results: The platform seeking latency and time to cross the original platform in the low-dose group and the high-dose group on the 3rd and 7th day of treatment were less than the model group(P<0.05), and the serum malondialdehyde (MDA) content were lower than that of the control group(P<0.05), the activity of superoxide dismutase (SOD) were higher than that of the model group(P<0.05), and there were no significant difference compared between the low-dose group and the high-dose group (P>0.05). The brain tissue cell index of the low-dose group and the high-dose group on the 7th day of treatment were higher than that of the model group(P<0.05), the relative expression levels of Bcl-2 and NF-κB p65 protein were lower than the model group (P<0.05), and there were no significant difference compared between the low-dose group and the high-dose group(P>0.05). Conclusions: The application of low-dose phenobarbital sodium in rats with ischemic brain injury can inhibit the expression of Bcl-2, NF-κB p65 protein, can also inhibit cell apoptosis in brain tissue, and can promote the release and decrease of SOD The content of MDA, so it is beneficial to promote the recovery of learning memory and working memory in rats. [ABSTRACT FROM AUTHOR]

This research was developed to investigate the effect of artificial intelligence neural network-based magnetic resonance imaging (MRI) image segmentation on the neurological function of patients with acute cerebral infarction treated with butylphthalide combined with edaravone. Eighty patients with acute cerebral infarction were selected as the research subjects, and the MRI images of patients with acute cerebral infarction were segmented by convolutional neural networks (CNN) upgraded algorithm model. MRI images of patients before and after treatment of butylphthalide combined with edaravone were compared to comprehensively evaluate the efficacy of this treatment. The results showed that compared with the traditional CNN algorithm, the running time of the CNN upgraded algorithm adopted in this study was significantly shorter, and the Loss value was lower than that of the traditional CNN model. Upgraded CNN model can realize accurate segmentation of cerebral infarction lesions in MRI images of patients. In addition, the degree of cerebral infarction and the degree of arterial stenosis were significantly improved after treatment with butylphthalide and edaravone. Compared with that before treatment, the number of patients with severe cerebral infarction or even vascular stenosis decreased significantly (P < 0.05), and gradually changed to mild vascular stenosis, and the neurological dysfunction of patients was also significantly improved. In short, MRI image segmentation based on artificial intelligence neural network can well-evaluate the efficacy and neurological impairment of butylphthalide combined with edaravone in the treatment of acute cerebral infarction, and it was worthy of promotion in clinical evaluation of the treatment effect of acute cerebral infarction. [ABSTRACT FROM AUTHOR]

The Center of Biomedical Research Excellence (COBRE) Center for Central Nervous System Function (CCNSF) was funded in 2013 by the National Institute for General Medical Sciences to establish a collaborative environment for basic and applied research in higher nervous system function with humans and experimental animal model systems. Since its inception, the COBRE CCNSF has funded junior faculty investigators as Project and Pilot Project Leaders and one established investigator on projects investigating fundamental properties of nervous system function using a range of tools spanning molecular genetics, neurophysiology, invasive and non-invasive brain stimulation, behavior and neuroimaging. The Administrative Core facilitates all Center activities with a focus on career development, grant proposal submission, and deployment of technology developed by our research cores. The Design and Analysis Core aims to provide principled study design expertise, statistical modeling, machine learning, inference, and computation. The Behavior and Neuroimaging Core provides project-specific collaboration and support to COBRE scientists to promote the acquisition of high quality behavioral, physiological, neuroimaging and neurostimulation data, to ensure the integrity of the data collection infrastructure and to help implement robust data processing and visualization pipelines. While the cores principally serve Center scientists, our Center and the core resources have availability to all Rhode Island researchers. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of variable durations of stretching on neural function, pain, and algometric pressure in patients with chronic myofascial pain syndrome. Design: Randomized controlled trial. Patients: A total of 100 participants diagnosed with chronic myofascial pain syndrome were randomly assigned to a control group or 1 of 3 intervention groups. Methods: The 3 experimental groups received different durations of cervical spine stretching: 15, 30 or 60 s. The control group did not stretch. Primary outcome measures included peak-to-peak somatosensory-evoked potential for dermatomes C6, C7 and C8. Secondary outcome measures included central somatosensory conduction time (N13–N20), pain intensity, and pressure-pain threshold algometric measurements. All outcome measures were assessed immediately after and 2 h after the treatment session. Results: Post hoc analysis indicated that stretching for 60 s significantly decreased the dermatomal amplitude for C6, C7 and C8 (p

Non-syndromic intellectual disability (NS-ID or idiopathic) is a complex neurodevelopmental disorder that represents a global health issue. Although many efforts have been made to characterize it and distinguish it from syndromic intellectual disability (S-ID), the highly heterogeneous aspect of this disorder makes it difficult to understand its etiology. Long noncoding RNAs (lncRNAs) comprise a large group of transcripts that can act through various mechanisms and be involved in important neurodevelopmental processes. In this sense, comprehending the roles they play in this intricate context is a valuable way of getting new insights about how NS-ID can arise and develop. In this review, we attempt to bring together knowledge available in the literature about lncRNAs involved with molecular and cellular pathways already described in intellectual disability and neural function, to better understand their relevance in NS-ID and the regulatory complexity of this disorder. [ABSTRACT FROM AUTHOR]

A total of 74 patients with ACI in our hospital were selected as the research objects. According to the National Institutes of Health Stroke Scale (NIHSS) score, they were divided into severe group (NIHSS score >15 points, n = 21), moderate group (NIHSS score 5-15 points, n=24), and mild group (NIHSS score <5 points, n=29). All received the detection of serum copeptin, IL-18 levels and spiral CT imaging. The results showed that with the aggravation of ACI neurological deficits, serum copeptin and interleukin 18 (IL-18) levels and peak time increased, while CBV and CBF decreased abnormally. The ROC curve showed that the area under the curve (AUC) of serum IL-18 combined with CBF to predict poor prognosis of ACI patients was the largest. It can be seen that there is a certain correlation between spiral CT imaging parameters, serum copeptin, IL-18 and the neurological function of ACI patients. The combination of the three provides the possibility to achieve individualized treatment of ACI patients and improve the prognosis. [ABSTRACT FROM AUTHOR]

Accumulating evidence has suggested that prenatal exposure to methadone causes multiple adverse effects on human brain development. Methadone not only suppresses fetal neurobehavior and alters neural maturation, but also leads to long-term neurological impairment. Due to logistical and ethical issues of accessing human fetal tissue, the effect of methadone on brain development and its underlying mechanisms have not been investigated adequately and are therefore not fully understood. Here, we use human cortical organoids which resemble fetal brain development to examine the effect of methadone on neuronal function and maturation during early development. During development, cortical organoids that are exposed to clinically relevant concentrations of methadone exhibited suppressed maturation of neuronal function. For example, organoids developed from 12th week till 24th week have an about 7-fold increase in AP firing frequency, but only half and a third of this increase was found in organoids exposed to 1 and 10 μM methadone, respectively. We further demonstrated substantial increases in INa (4.5-fold) and IKD (10.8-fold), and continued shifts of Na+ channel activation and inactivation during normal organoid development. Methadone-induced suppression of neuronal function was attributed to the attenuated increase in the densities of INa and IKD and the reduced shift of Na+ channel gating properties. Since normal neuronal electrophysiology and ion channel function are critical for regulating brain development, we believe that the effect of prolonged methadone exposure contributes to the delayed maturation, development fetal brain and potentially for longer term neurologic deficits.

The present study aimed to investigate the effects of levetiracetam tablets and lacosamide (LCM) on therapeutic efficacy and neural function in patients with epilepsy. We assigned 252 patients with refractory partial seizures admitted to our hospital to receive either levetiracetam tablets [120 patients, the control group (CG)] or levetiracetam tablets combined with LCM [132 patients, the joint group (JG)]. The bone mineral density and neural function between the two groups at 6 months before and after treatment were compared. The total response rate was higher in the JG than in the CG (P<0.05). There was no significant difference in the comparison of the multiple indexes between the two groups before treatment (P>0.05). The frequency of seizures was reduced after treatment in the two groups, however, it was lower in the JG compared with the CG (P<0.05). The levels of neurological indicators were significantly reduced after treatment in the two groups (P<0.05), however, the reduction was more marked in the JG than in the CG. The bone mineral density (BMD) of the femoral neck decreased after treatment in the two groups (P<0.05), but there was no difference between the two groups after treatment (P>0.05). The calcium content decreased after treatment in the two groups (P<0.05), but there was no difference between the two groups after treatment (P>0.05). The comparison of other bone metabolism markers between the two groups exhibited no significant differences. The combination therapy greatly increased the quality of life score and the 1-year drug retention rate. To sum up, levetiracetam tablets combined with LCM significantly enhanced the therapeutic effect and improved the neural function in patients with refractory partial seizures, however this therapy may cause a slight adverse effect on BMD and bone metabolism in the short term. [ABSTRACT FROM AUTHOR]

Background and purpose: The present study aimed to explore the feasibility and efficacy of the targeted non-invasive implantation of mesenchymal stromal cells (MSCs) by low-intensity ultrasound-targeted microbubble destruction (LI-UTMD) assisted blood–brain barrier (BBB) opening and its improvement on neurobehavioural outcomes in brain ischaemic rats. Methods: A transcranial irradiation of low-intensity ultrasound by diagnostic devices was performed, and lipid microbubbles (MBs) and MSCs were simultaneously infused. Then, the MSC transmigration from brain vessels to parenchyma was demonstrated, and MSCs were statistically analysed on days 1, 4, 7 and 14. Behavioural function was statistically analysed. Results: The extra-vascular leakage of lanthanum and EB was observed at the brain ischaemic area receiving ultrasound. MSCs were observed at the ultrasound irradiated brain hemisphere, and the number of MSCs in LI-UTMD assisted MSCs group was significantly higher than that in the MSCs group (p <.01). The attachment, traversing and trans-migration of MSCs across the BBB were recorded. Neuro-behavioural function was improved with this approach. Conclusions: The transcranial irradiation of low intensity ultrasound targeted MBs destruction on brain ischaemic rats might be a safe and efficient BBB opening approach to prompt the successful delivery of MSCs into the targeted area of brain ischaemia, and ameliorate neurological function. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of adjuvant therapy with salviae miltiorrhizae and ligustrazine injection on neural function injury, degree of oxidative stress reaction, chemotactic factor and adhesion molecule in patients with ischemic stroke. Methods: Patients with ischemic stroke admitted in our hospital from August 2013 to October 2015 were retrospectively analyzed and divided into conventional treatment (CT) group receiving conventional treatment and traditional Chinese medicine auxiliary (TCMA) group receiving adjuvant therapy with salviae miltiorrhizae and ligustrazine injection. After the treatment of the first month and the third month, serum was collected to detect the contents of nerve injury molecules, oxidative stress parameters, chemotactic factor and adhesion molecule. >Results: After the 4-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1, CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients of TCMA group were all significantly lower than those of CT group, and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. After the 8-week treatment, the contents of serum neuron specific enolase, S100 calcium-binding protein B, heart-type fatty acid binding protein, malondialdehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine, monocyte chemoattractant protein-1, CD40, CD40 ligand, vascular endothelial cadherin, soluble intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1 in patients of TCMA group were all significantly lower than those of CT group and the contents of superoxidase dismutase, glutathione peroxidase and catalase were significantly higher than those of CT group. >Conclusions: Adjuvant therapy with salviae miltiorrhizae and ligustrazine injection can alleviate the neural function injury, inhibit oxidative stress reaction and the generation of chemotactic factor and adhesion molecule in patients with ischemic stroke, which is an effective medicine for treating ischemic stroke.

Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.

Non-syndromic intellectual disability (NS-ID or idiopathic) is a complex neurodevelopmental disorder that represents a global health issue. Although many efforts have been made to characterize it and distinguish it from syndromic intellectual disability (S-ID), the highly heterogeneous aspect of this disorder makes it difficult to understand its etiology. Long noncoding RNAs (lncRNAs) comprise a large group of transcripts that can act through various mechanisms and be involved in important neurodevelopmental processes. In this sense, comprehending the roles they play in this intricate context is a valuable way of getting new insights about how NS-ID can arise and develop. In this review, we attempt to bring together knowledge available in the literature about lncRNAs involved with molecular and cellular pathways already described in intellectual disability and neural function, to better understand their relevance in NS-ID and the regulatory complexity of this disorder.

The objective of the present study was to explore the effects of early repair of traumatic craniocerebral injury on neural functions, as well as the optimal extraction of medical information from craniocerebral injury images. Therefore, a total of 60 patients with traumatic craniocerebral injury were submitted to decompressive craniectomy and then cranioplasty. Afterward, all the patients were divided into the early group and the routine group. The changes in indicators of both groups after the patients underwent decompressive craniectomy were compared and retrospectively analysed. The National Institutes of Health stroke scale, Karnofsky performance status, and the Glasgow outcome scale scores in the 1st, 3rd, and 12th months after decompressive craniectomy of patients were observed. In terms of medical image information extraction, based on the active contour models of global region, the information was extracted from segmentation weak boundary images to quickly, completely, and clearly obtain the images of the cerebral region of patients with a traumatic craniocerebral injury. The results showed that the Glasgow outcome scale, Karnofsky performance status, and National Institutes of Health stroke scale scores of the early group were 3.23±0.67, 52.23±7.54, and 6.75±0.23, respectively. The Glasgow outcome scale, Karnofsky performance status and National Institutes of Health stroke scale scores of the routine group were 2.94±0.37, 51.42±4.68, and 6.32±0.24, respectively. The data of both groups were compared and the differences were not statistically significant. In the early group, the Glasgow outcome scale and National Institutes of Health stroke scores in the 6th month after trauma were 3.67±0.682 and 13.84±4.789, respectively, while in the routine group, these were 3.29±0.714 and 17.02±6.453, respectively and the differences were significant. It can be seen from the experimental results of extracting the target segmentation information that although the algorithm adds noise to the original image, it could accurately segment and extract the target region with little noise. It was not necessary to consider the selection of the initialization target, and the iteration could improve the segmentation efficiency of the algorithm. Also, it was found that given the condition of well-handled preoperative and preoperative indications, the early repair can promote the repair of neural functions of patients. Moreover, a contour model algorithm was proposed, which could effectively extract the medical information of the craniocerebral injury images, providing powerful theoretical guidance for the development of craniocerebral medical image information technology. [ABSTRACT FROM AUTHOR]

In this paper, I argue that looking at the concept of neural function through the lens of cognition alone risks cognitive myopia: it leads neuroscientists to focus only on mechanisms with cognitive functions that process behaviorally relevant information when conceptualizing “neural function”. Cognitive myopia tempts researchers to neglect neural mechanisms with noncognitive functions which do not process behaviorally relevant information but maintain and repair neural and other systems of the body. Cognitive myopia similarly affects philosophy of neuroscience because scholars overlook noncognitive functions when analyzing issues surrounding e.g., functional decomposition or the multifunctionality of neural structures. I argue that we can overcome cognitive myopia by adopting a patchwork approach that articulates cognitive and noncognitive “patches” of the concept of neural function. Cognitive patches describe mechanisms with causally specific effects on cognition and behavior which are likely operative in transforming sensory or other inputs into motor outputs. Noncognitive patches describe mechanisms that lack such specific effects; these mechanisms are enabling conditions for cognitive functions to occur. I use these distinctions to characterize two noncognitive functions at the mesoscale of neural circuits: subsistence functions like breathing are implemented by central pattern generators and are necessary to maintain the life of the organism. Infrastructural functions like gain control are implemented by canonical microcircuits and prevent neural system damage while cognitive processing occurs. By adding conceptual patches that describe these functions, a patchwork approach can overcome cognitive myopia and help us explain how the brain’s capacities as an information processing device are constrained by its ability to maintain and repair itself as a physiological apparatus. [ABSTRACT FROM AUTHOR]

Functional networks (FNs) have shown excellent performance in probability, statistics, engineering applications, etc., but so far no methods of direct sequence estimation (DSE) for communication systems using FN have been published. The paper presents a new DSE approach using FN, which can be applied to cases with plural source signal sequence, short sequence or even the absence of training sequence. The proposed method can estimate the source sequence directly from the observed output data without training sequence and pre-estimating the channel impulse response. Firstly, a multiple-input multiple-output FN (MIMOFN), in which the initial input vector is devised via QR decomposition of receiving signal matrix, is adopted to solve the special issue. Meantime, a design method of the neural function for this special MIMOFN is proposed. Then, the learning rule for the parameters of neural functions is trained and updated by back-propagation learning algorithm. Finally, a simulation experiment is performed, the feasibility and accuracy of the method are showed from the experimental results, and some special simulation phenomena of the algorithm are observed. [ABSTRACT FROM AUTHOR]

Taurine is a highly abundant “amino acid” in the brain. Although the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish ( Danio rerio ) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action. In this context, we also highlight how zebrafish models of brain disorders may present interesting approaches to assess molecular mechanisms underlying positive effects of taurine in the brain. Finally, we outline recent advances in zebrafish drug screening that significantly improve neuropsychiatric translational research and small molecule screens. [ABSTRACT FROM AUTHOR]

Abstract: Perhexiline, a chiral drug, is a potent antiischemic agent whose clinical utility is limited by hepatic and neural toxicities. It inhibits mitochondrial carnitine palmitoyltransferase‐1, however, excessive inhibition predisposes toward tissue steatosis. This pilot study investigated the distribution of the two enantiomers and their toxicological potential. Dark Agouti rats (n = 4 per group) were administered vehicle or 200 mg/kg daily of racemic, (+)− or (−)‐perhexiline maleate orally for 8 weeks. Plasma biochemical liver function tests and Von Frey assessments of peripheral neural function were performed. Hepatic and neuronal histology, including lipid and glycogen content, was assessed using electron microscopy. Concentrations of the perhexiline enantiomers and metabolites were quantified in plasma, liver and heart. Plasma perhexiline concentrations following administration of racemate, (+)− or (‐)‐enantiomer were within the mid‐upper clinical therapeutic range. There was extensive uptake of both enantiomers into liver and heart, with 2.5‐ to 4.5‐fold greater net uptake of (+)‐ compared to (−)‐perhexiline (P < .05) when administered as pure enantiomers, but not when administered as racemate. There was no biochemical or gross histological evidence of hepatotoxicity. However, livers of animals administered (+)‐perhexiline had higher lipid (P < .01) and lower glycogen (P < .05) content, compared to those administered (−)‐perhexiline. Animals administered racemic perhexiline had reduced peripheral neural function (P < .05) compared to controls or animals administered (−)‐perhexiline. For the same plasma concentrations, differences in tissue distribution may contribute to disparities in the effects of (+)‐ and (−)‐perhexiline on hepatic histology and neural function. [ABSTRACT FROM AUTHOR]

Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML-RARa and RARa-PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2-1 µm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs). Dysregulation of PML NB formation results in altered transcriptional regulation, protein modification, apoptosis and cellular senescence. In addition to PML NBs, PML is also present in nucleoplasm and cytoplasmic compartments, including the endoplasmic reticulum and mitochondria-associated membranes. The role of PML in tumor suppression has been extensively studied but increasing evidence indicates that PML also plays versatile roles in stem cell renewal, metabolism, inflammatory responses, neural function, mammary development and angiogenesis. In this review, we will briefly describe the known PML regulation and function and include new findings. [ABSTRACT FROM AUTHOR]

Taurine is a highly abundant “amino acid” in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish ( Danio rerio ) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action. In this context, we also highlight how zebrafish models of brain disorders may present interesting approaches to assess molecular mechanisms underlying positive effects of taurine in the brain. Finally, we outline recent advances in zebrafish drug screening that significantly improve neuropsychiatric translational researches and small molecule screens. [ABSTRACT FROM AUTHOR]

(Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors. Release of GABA from inhibitory interneurons at the olfactory bulb induces inhibitory currents at the mitral cells, which are output neurons from the olfactory bulb. (Design) In the present study, we measured spontaneous inhibitory postsynaptic currents (sIPSCs) at the mitral cells of mice fed a soft diet in order to explore the effects of changes in texture of diets on neural function at the olfactory bulb. (Results) The soft-diet feeding extended the intervals between sIPSCs and reduced their peak amplitudes. (Conclusions) The present results suggest that soft-diet feeding in mice attenuates the neural functions of inhibitory interneurons at the olfactory bulb. [ABSTRACT FROM AUTHOR]