BMC Neuroscience最新文献

{"title":"Epigallocatechin -3- gallate mitigates diazinon neurotoxicity via suppression of pro-inflammatory genes and upregulation of antioxidant pathways.","authors":"Charles Etang Onukak, Omowumi Moromoke Femi-Akinlosotu, Adedunsola Adewunmi Obasa, Oluwabusayo Racheal Folarin, Temitayo Olabisi Ajibade, Olumayowa Olawumi Igado, Oluwaseun Olarenwaju Esan, Taiwo Olaide Oyagbemi, Adewunmi Victoria Adeogun, Ademola Adetokunbo Oyagbemi, Olufunke Eunice Ola-Davies, Temidayo Olutayo Omobowale, James Olukayode Olopade, Oluwafemi Omoniyi Oguntibeju, Momoh Audu Yakubu","doi":"10.1186/s12868-025-00943-x","DOIUrl":"10.1186/s12868-025-00943-x","url":null,"abstract":"<p><p>Diazinon is a commonly used organophosphate (OP) insecticide especially in developing countries for the control of insect pests, however, exposure to its toxic impact especially in humans and other non-target species remains an important public health concern. The study aimed to investigate the effect of epigallocatechin -3- gallate (EGCG), abundant in green tea plants on neurobehavioural, biochemical, and pathological changes in the brain of male Wistar rats following exposure to diazinon toxicity. Sixty adult male Wistar rats were acclimatized for seven days and subsequently randomly assigned into six treatment groups as follows: Group I: Control group (0.2 mL distilled water); Group II: Diazinon at 3 mg/kg (1% LD50); Group III: Diazinon (3 mg/kg) + EGCG (50 mg/kg, ~ 2% of LD50); Group IV: Diazinon (3 mg/kg) + EGCG (100 mg/kg, ~ 5% of LD50); Group V: EGCG (50 mg/kg) and Group VI: EGCG (100 mg/kg). All treatments were administered orally once daily for 14 days. Neurobehavioural studies, biomarkers of oxidative stress, histology, immunohistochemistry, and quantitative polymerase chain reaction (RT qPCR) were performed. Diazinon alone impaired recognition memory, increased oxidative stress markers and altered antioxidant defense in the brain. It upregulated TNF-α and IL-6 genes and repressed GPx 4 gene expressions. It was also associated with increased GFAP, Tau, and α-SN immunoreactivity. Microscopic examination revealed loss of Purkinje and hippocampal cells in brain. Co-treatment with EGCG however improved cognition, lowered oxidative stress markers, improved antioxidant status and suppressed TNF-α and IL-6. In conclusion, findings from this study demonstrated that EGCG offered protection against diazinon-induced neurotoxicity. Hence, natural sources of epigallocatechin -3- gallate such as fruits and vegetables could offer immense benefits by protecting against oxidative stress and inflammation in neurodegenerative disease conditions.Clinical trial number Not applicable.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"22"},"PeriodicalIF":2.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick's disease and fronto-temporal tauopathies.","authors":"Edward Rockenstein, Kiren Ubhi, Michael Mante, Jazmin Florio, Anthony Adame, Stefan Winter, Hemma Brandstaetter, Dieter Meier, Eliezer Masliah","doi":"10.1186/s12868-025-00942-y","DOIUrl":"10.1186/s12868-025-00942-y","url":null,"abstract":"","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"23"},"PeriodicalIF":2.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine attenuates traumatic brain injury by modulating STAT3-mediated Glycolysis and immune responses.","authors":"Yufang Liu, Zheng Gong, Longfei Zhang, Xian Yang, Jie Zhu, Xin Zhou, Xingzhi Liao","doi":"10.1186/s12868-025-00941-z","DOIUrl":"10.1186/s12868-025-00941-z","url":null,"abstract":"<p><strong>Background: </strong>Secondary injury following traumatic brain injury (TBI) involves neuroinflammation, immune cell infiltration, and metabolic dysregulation, leading to progressive neurological damage. This study evaluates the potential of esketamine, an NMDA receptor antagonist, to modulate immune responses, inhibit glycolysis, and mitigate secondary brain injury in a TBI mouse model.</p><p><strong>Methods: </strong>Male C57BL/6J mice were subjected to controlled cortical impact to induce TBI. Mice were treated with esketamine, either alone or combined with the STAT3 activator colivelin, or the glycolysis inhibitor 2-deoxyglucose (2-DG). Neurological function, BBB permeability, immune cell infiltration, macrophage polarization, and glycolytic activity were assessed using immunohistochemistry, flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Esketamine treatment significantly reduced structural brain tissue damage, including contusions, tissue loss, and edema, while also improving neurological outcomes in TBI mice. Mechanistically, esketamine inhibited CD4 + T cell activation and suppressed Th17 differentiation both in vivo and in vitro. It also promoted a shift in macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Further analysis revealed that esketamine blocked STAT3 activation, which in turn reduced the expression of glycolytic genes (e.g., Hk2, Pgk1, Aldoa) essential for Th17 cell proliferation and M1 polarization. Co-treatment with colivelin reversed esketamine's effects on STAT3-mediated glycolysis, while 2-DG enhanced its anti-inflammatory actions.</p><p><strong>Conclusion: </strong>Esketamine attenuates TBI-induced neuroinflammation and tissue damage by inhibiting STAT3-mediated glycolysis, thus reducing Th17 and M1 macrophage activity and promoting regulatory and reparative immune responses. These findings highlight esketamine's potential as a therapeutic option for TBI, targeting both immune modulation and metabolic pathways to alleviate secondary injury.</p><p><strong>Clinical trial number: </strong>not applicable.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"21"},"PeriodicalIF":2.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The changes of digestive system inflammatory, oxidative stress, and histopathology factors following oral mesenchymal stem cells administration in rats with traumatic brain injury.","authors":"Masoud Eslami, Alireza Raji-Amirhasani, Mohammad Khaksari, Zakieh Keshavarzi, Farzaneh Rostamzadeh, Nazanin Sabet, Elham Jafari, Zahra Soltani, Saeed Karamouzian","doi":"10.1186/s12868-025-00936-w","DOIUrl":"10.1186/s12868-025-00936-w","url":null,"abstract":"<p><strong>Background and aims: </strong>Mucous mesenchymal stem cells can migrate to damaged areas, and their use is proposed as a new approach to treating diseases. The present study aimed to investigate the effect of oral mesenchymal stem cells (OMSCs) on inflammatory, oxidative stress, and histopathological indices in the tissues of the stomach, intestine, and colon after traumatic brain injury (TBI).</p><p><strong>Methods and materials: </strong>Adult male rats were randomly divided into four groups: Sham, TBI, Vehicle (Veh), and Stem cell (SC). Intravenous injection of OMSCs was performed at 1 and 24 h after injury. The inflammatory, oxidative stress, and histopathological indices of the tissues of the stomach, small intestine, and colon were evaluated 48 h after injury.</p><p><strong>Results: </strong>After TBI, IL-1β and IL-6 levels increased and IL-10 levels decreased in the tissues of the stomach, small intestine, and colon, but the administration of OMSCS prevented these changes to a large extent. Oxidative stress indices (MDA, PC, TAC, SOD, and CAT) showed an increase in oxidative stress after TBI, but oxidative stress was less severe in the OMSC group. The administration of OMSCs after TBI improved the histopathological outcome in the tissues of the stomach, small intestine, and colon.</p><p><strong>Conclusion: </strong>Administration of OMSCs in rats suffering from TBI can improve inflammatory, oxidative stress, and histopathological indices in the tissues of the stomach, small intestine, and colon, which shows the beneficial effect of using OMSCs in TBI.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"20"},"PeriodicalIF":2.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.","authors":"Hoang Kieu Chi Ngo, Akriti Srivastava, Hoang Le, Samuel J Ayer, Grace F Crotty, Michael A Schwarzschild, Rachit Bakshi","doi":"10.1186/s12868-025-00939-7","DOIUrl":"10.1186/s12868-025-00939-7","url":null,"abstract":"<p><strong>Background: </strong>The G2019S mutation of LRRK2, which enhances kinase activity of the protein, confers a substantial risk of developing Parkinson's disease (PD). However, the mutation demonstrates incomplete penetrance, suggesting the involvement of other genetic or environmental modulating factors. Here, we investigated whether LRRK2 G2019S knock-in (KI) mice treated with the inflammogen lipopolysaccharide (LPS) could model LRRK2 PD.</p><p><strong>Results: </strong>We found that short-term (2 weeks) treatment with LPS did not result in the loss of dopaminergic neurons in either LRRK2 G2019S KI or wild-type (WT) mice. Compared with WT mice, LRRK2 G2019S-KI mice showed incomplete recovery from LPS-induced weight loss. In LRRK2 G2019S KI mice, LPS treatment led to upregulated phosphorylation of LRRK2 at the autophosphorylation site Serine 1292, which is known as a direct readout of LRRK2 kinase activity. LPS treatment caused a greater increase in the activated astrocyte marker glial fibrillary acidic protein (GFAP) in the striatum and substantia nigra of LRRK2 G2019S mice than in those of WT mice. The administration of caffeine, which was recently identified as a biomarker of resistance to developing PD in individuals with LRRK2 mutations, attenuated LPS-induced astrocyte activation specifically in LRRK2 G2019S KI mice.</p><p><strong>Conclusions: </strong>Our findings suggest that 2 weeks of exposure to LPS is not sufficient to cause dopaminergic neuronal loss in LRRK2 G2019S KI mice but rather results in increased astrocyte activation, which can be ameliorated by caffeine.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"19"},"PeriodicalIF":2.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization of perivascular spaces in the human brain with 5-T magnetic resonance imaging.","authors":"Sirui Liu, Jianbo Li, Rui Hua, Yaowen Xing, Jiaojiao Wu, Jiang Lin, Jian Wang, Yan Shan, Lei Xu, Feng Shi, Mengsu Zeng","doi":"10.1186/s12868-025-00925-z","DOIUrl":"10.1186/s12868-025-00925-z","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the effectiveness of 5-Tesla (T) magnetic resonance imaging (MRI) in the visualization of perivascular spaces (PVS).</p><p><strong>Method: </strong>A total of seventeen subjects underwent three-dimensional (3D) T1- and T2-weighted imaging on both 3-T and 5-T MRI systems. Twelve of these subjects underwent quantitative analysis of PVS in the semioval center (SOC) and basal ganglia (BG), with comparisons made between the two systems using paired-sample Wilcoxon tests. Additionally, high-resolution 5-T images were acquired for five other participants to examine the detailed anatomy of PVS in the SOC, BG, and cerebral cortex.</p><p><strong>Results: </strong>Compared with 3-T MRI, 5-T MRI detected more PVS in the SOC and BG [39.5 (32.0-63.0) vs. 56.5 (44.0-75.5) and 49.5 (27.0-55.8) vs. 65.5 (53.0-72.0)] with p-values of 0.002 and 0.004, respectively. In these two regions, the PVS tortuosity, defined as the ratio of the actual path length to the straight-line distance between the start and end points of the PVS, was lower at 3-T compared to 5-T (p = 0.012 for the SOC and p = 0.006 for the BG). The length of PVS in the SOC on 5-T was longer than those on 3-T [4.6 mm (3.9-6.3 mm) vs. 5.1 mm (4.6-6.7 mm), p = 0.049]. In addition, the 5-T MRI provided enhanced visualization of the morphology of PVS in vivo, and improved the depiction of PVS across various brain regions, especially in the cortex, illustrating their course and associated small vessels.</p><p><strong>Conclusions: </strong>5-T MRI notably enhanced the visualization of PVS compared to 3-T, particularly in its ability to depict PVS anatomy in the cortex using high-resolution images. This advancement may pave the way for further research into the physiological roles of PVS and their involvement in related diseases.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"18"},"PeriodicalIF":2.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models.","authors":"Musaab Abdulrazzaq Qader, Leila Hosseini, Nasrin Abolhasanpour, Farnaz Oghbaei, Leila Maghsoumi-Norouzabad, Hanieh Salehi-Pourmehr, Fatemeh Fattahi, Reza Naghdi Sadeh","doi":"10.1186/s12868-025-00937-9","DOIUrl":"10.1186/s12868-025-00937-9","url":null,"abstract":"<p><p>This systematic review sought to assess the impact of nicotinamide adenine dinucleotide (NAD⁺) precursors on cognitive impairments in several diseases in rat/mouse models. Accumulating evidence suggests that inflammation, apoptosis, oxidative stress responses, and mitochondrial dysfunction are potential factors of cognitive deficits in aging, Alzheimer's disease (AD), diabetes, traumatic brain injury (TBI), vascular dementia (VAD), and schizophrenia. NAD⁺ precursors have received increased interest due to their unique molecular structure targets antioxidant and inflammatory pathways and mitochondrial function. The PubMed, Scopus, Google Scholar, Embase, and Web of Science databases were searched through May 30, 2024. Studies investigating the effect of NAD⁺ precursors on cognitive impairments in rodent models were included. Two reviewers independently extracted and evaluated the data. The PRISMA guidelines for reporting systematic reviews were followed. Thirty preclinical studies were included in the review. Studies have revealed that treatment with NAD⁺ rescues cognitive deficits by inhibiting inflammation, oxidative stress, and apoptosis and improving mitochondrial function. Preclinical evidence has demonstrated that treatment with NAD⁺ precursors may be more effective in learning and memory recovery in AD, TBI, diabetes, aging, VAD, and schizophrenia. The outcomes of this investigation may lead to additional studies on the use of NAD⁺ precursors for treating human cognitive decline.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"17"},"PeriodicalIF":2.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of multisystem exercises on balance, postural stability, mobility, walking speed, and pain in patients with diabetic peripheral neuropathy: a randomized controlled trial.","authors":"Sidra Khurshid, Aruba Saeed, Muhammad Kashif, Aniqa Nasreen, Huma Riaz","doi":"10.1186/s12868-024-00924-6","DOIUrl":"10.1186/s12868-024-00924-6","url":null,"abstract":"<p><strong>Background: </strong>Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, is associated with peripheral nerve damage, leading to balance impairments, postural instability, and reduced mobility. Addressing these challenges requires comprehensive interventions that target multiple deficits simultaneously. Evidence suggests that exercise programs combining balance, proprioception, strength, and reaction time training can improve postural stability, enhance mobility, and alleviate pain in individuals with DPN.</p><p><strong>Objective: </strong>The objective of this study was to compare the effects of multisystem exercises and conventional exercises on balance, postural stability, mobility, and walking speed and to reduce pain in patients with diabetic peripheral neuropathy.</p><p><strong>Methods: </strong>This double-blinded, two-arm parallel design randomized controlled trial was conducted at DHQ Hospital, Pakpattan, Pakistan. A total of 50 participants who met the inclusion criteria were recruited using the nonprobability convenience sampling technique. They were randomly assigned to either a multisystem physical exercise (MPE) group (n = 26) and a conventional exercise group (n = 24). The MPE program included balance, proprioception, strength, and reaction time training, while the control group received conventional exercises, consisted of strength, balance, stretching, and range of motion exercises. Both groups underwent 30 min intervention sessions, 3 times per week, for 8 weeks. The outcome measures used for assessing the balance, postural stability, mobility, and pain included the Berg balance scale (BBS), functional reach test (FRT), time up and go test (TUG), 10 min walk test (10-MWT), and numeric pain rating scale (NPRS). The data was analyzed using SPSS version 26.</p><p><strong>Results: </strong>Significant group and time interactions were observed for all outcome measures including BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.001). The between-group analysis also revealed significant differences between the multisystem physical exercise group and the conventional exercise group at both the 4th week and 8th week for BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.05).</p><p><strong>Conclusion: </strong>The study concluded that multisystem exercises resulted in significant improvement in balance, postural stability, mobility, and walking speed, along with reduction in pain, compared to conventional exercises in patients with diabetic peripheral neuropathy.</p><p><strong>Trial registration: </strong>This randomized controlled study was registered prospectively on November 11th, 2023 with the ClinicalTrials.gov (NCT06130917).</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"16"},"PeriodicalIF":2.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social isolation induces sexually aggressive behaviour in male Wistar rats.","authors":"Mbiydzenyuy Elvis Ngala, Sian Megan Joanna Hemmings, Jacqueline Samantha Womersley, Thando W Shabangu, Lihle Qulu-Appiah","doi":"10.1186/s12868-025-00932-0","DOIUrl":"10.1186/s12868-025-00932-0","url":null,"abstract":"<p><strong>Background: </strong>Sexual violence, a pervasive global issue, significantly impacts individuals and societies, necessitating a deeper understanding of its underlying biological mechanisms. This study aimed to elucidate the role of stress-induced dysregulation of the hypothalamus-pituitary-adrenocortical axis in sexual aggression in male Wistar rats. Employing a sexual aggression paradigm, we investigated the effects of social isolation on aggression, anxiety-like behaviour, and neurochemistry in virgin adult male Wistar rats.</p><p><strong>Results: </strong>The results showed that social isolation significantly escalated aggressive behaviours and induced anxiety-like responses in male rats. The sexual aggression test revealed that socially isolated males exhibited heightened aggression towards non-receptive females. Neurochemical analyses indicated significant alterations in key markers, such as corticotrophin-releasing hormone, oxytocin, and arginine vasopressin, correlating with the observed behavioural changes. Gene expression analyses revealed significant findings, particularly in the expression of the oxytocin receptor (OXTR) and vasopressin receptor 1 A (AVPR1A) genes. Social isolation and the duration of aggressive behaviour prior to the sexual aggression test significantly influenced OXTR expression in the hippocampus and AVPR1A expression in both the prefrontal cortex and hippocampus, highlighting the complex interplay between environmental stressors, neurochemical responses, and gene expression in the manifestation of sexual aggression behaviour.</p><p><strong>Conclusions: </strong>This study underscores the critical impact of stress and social isolation on sexual aggression, providing valuable insights into possible neurobiological underpinnings of sexual violence. Understanding these mechanisms is crucial for developing effective interventions to mitigate the consequences of sexual aggression.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"15"},"PeriodicalIF":2.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventromedial hypothalamic nucleus neuronal nitric oxide knockdown effects on GABAergic neuron metabolic sensor and transmitter marker gene expression in the male rat.","authors":"Sagor C Roy, Madhu Babu Pasula, Subash Sapkota, Karen P Briski","doi":"10.1186/s12868-025-00940-0","DOIUrl":"10.1186/s12868-025-00940-0","url":null,"abstract":"<p><p>The diffusible gas nitric oxide (NO) and amino acid γ-gamma-aminobutyric acid (GABA) exert contrary effects on glucose counterregulation in the male rat, but how these neurochemical signals integrate within ventromedial hypothalamic nucleus (VMN) neural circuitries remains unclear. Female rat dorsomedial (VMNdm) and ventrolateral (VMNvl) GABAergic neurons express neuronal nitric oxide synthase (nNOS) mRNA; notably these subpopulations exhibit dissimilar nNOS transcriptional responses to insulin-induced hypoglycemia (IIH). Here, nNOS gene knockdown tools were used to examine whether one or both VMN GABA neuron groups may be a target for nitrergic control of basal and hypoglycemic counterregulatory hormone secretion in the male. Data show that VMN nNOS gene knockdown respectively up- or down-regulated counterregulatory hormone profiles in eu- versus hypoglycemic male rats. Single-cell multiplex qPCR analysis of laser-catapult-microdissected GABA neurons showed that IIH elevated nNOS gene expression in GABA neurons from each VMN division, yet nNOS siRNA pretreatment attenuated distinctive IIH-associated transmitter marker gene expression patterns in VMNdm versus VMNvl GABAergic neurons. nNOS gene silencing had similar effects on glucokinase and glucose transporter gene responses to IIH in each GABA neuron subpopulation but elicited division-specific effects on mRNA encoding 5-AMP-activated protein kinase (AMPK) alpha/catalytic subunits and the lactate membrane receptor GPR81/HCAR1. Current findings provide original evidence that VMN NO may impose bi-directional, glucose status-contingent control of counterregulatory hormone outflow in the male rat. Data moreover imply that during IIH, NO may control distinctive sources of metabolic sensory regulatory stimuli in VMNdm versus VMNvl GABA neurons and may shape unique counterregulation-controlling neurochemical transmission by each cell population.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"14"},"PeriodicalIF":2.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}