Journal of integrative neuroscience最新文献

{"title":"Does Freediving Lead to Hippocampal Adaptability to Hypoxia and Maintenance of Episodic Memory?","authors":"Julia Micaux, Clément Poiret, Jingwen Zhao, Aya El Hajj, Morgane Tillenon, Abir Troudi Habibi, Franck Mauconduit, Fawzi Boumezbeur, Catherine Chiron, Marion Noulhiane","doi":"10.31083/JIN36672","DOIUrl":"https://doi.org/10.31083/JIN36672","url":null,"abstract":"<p><strong>Background: </strong>Accidental hypoxia has detrimental effects on the brain, particularly on the hippocampal subfields (HS), which are highly sensitive to oxygen deprivation and play a crucial role in episodic memory. This raises the question: could freediving training induce anatomical changes in the HS and lead to significant memory deficits? This study aimed to investigate the impact of a season of freediving training on HS anatomy and episodic memory performance, as freedivers represent a unique natural model for studying the effects of repeated voluntary hypoxic exposure on brain function in healthy individuals. Extending previous research, this study assessed these effects over a prolonged training period.</p><p><strong>Methods: </strong>Seventeen male freedivers were evaluated before and after 7 months of training and compared with a control group of 20 non-freediver athletes. HS anatomical volumes were measured using MRI segmentation and episodic memory performance was evaluated using a pattern separation (PS) task. This task specifically targeted HS-related memory processes by distinguishing between three types of items: (i) identical, (ii) similar, and (iii) new.</p><p><strong>Results: </strong>No significant differences were observed between freedivers and controls in HS volumes or memory performance, either before or after the 7 month training period. A two-way repeated measures ANOVA revealed that freedivers exhibited the same memory pattern as the control group in the PS task. Specifically, both groups performed better with (i) identical items compared with (ii) similar items (<i>p</i> < 0.001) and were less accurate with (ii) similar items compared with (iii) new items (<i>p</i> < 0.001). This aligns with expectations, as distinguishing similar items from previously presented ones is more cognitively demanding than recognizing new items.</p><p><strong>Conclusions: </strong>These findings suggest that repeated voluntary hypoxic exposure during freediving training does not impair episodic memory function. Freedivers' memory performance remained comparable with that of the control group, with no detectable adverse effects on hippocampal anatomy.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 7","pages":"36672"},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Change Associated with Anesthesia and Surgery: An Introduction to POCD for Neuroscientists.","authors":"Yang Li, Qiaoyi Peng, Jian Lu, Li Hu, Hongmei Zhou","doi":"10.31083/JIN36785","DOIUrl":"https://doi.org/10.31083/JIN36785","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a central nervous system (CNS) complication seen in elderly patients, characterized by a decline in memory, comprehension, and attention in patients after surgery and general anesthesia. The pathophysiologic mechanisms of postoperative cognitive dysfunction are not well understood and effective means of prevention and treatment are currently lacking. Basic and clinical research, including the use of pre-clinical animal models of POCD, is advancing rapidly. In this paper, we review and summarize various factors that contribute to the development of POCD, including oxidative stress, autophagy, impaired synaptic function, and neuroinflammation, and describe the construction of animal models of POCD. By analyzing the gap between clinical and basic research, we propose recommendations for clinically relevant animal model development and the conducting of clinical studies to better understand the mechanisms and etiology associated with POCD. We aim to enhance understanding of the occurrence of POCD and to provide a more comprehensive perspective on the prevention and treatment of POCD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 7","pages":"36785"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Improvement in Neck and Limb Motor Control Outcomes Following Treatment of the Upper Neck and Spine: A Repeated Measures Cohort Study.","authors":"Ushani Ambalavanar, Rufeyda Wise, Heidi Haavik, Bernadette A Murphy","doi":"10.31083/JIN39548","DOIUrl":"https://doi.org/10.31083/JIN39548","url":null,"abstract":"<p><strong>Background: </strong>Sensory feedback from the upper cervical regions is used by the central nervous system to stabilize the occipito-atlantal (C0-C1) joint for leveled vision and to assess head position, which is used in sensorimotor integration (SMI) of neck and upper limb motor control. However, few studies have specifically investigated the impact of C0-C1 dysfunction and/or its rectification on SMI related outcomes. This study sought to determine the impact of restricted C0-C1 mobility and musculoskeletal pain on neck and upper limb motor control, whether these motor control deficits persist without treatment, and whether motor control improves following treatment designed to improve C0-C1 mobility.</p><p><strong>Methods: </strong>Twenty-two participants with restricted C0-C1 mobility attended three data collection sessions (baseline, control (2 to 5 days later), and post-treatment) at a private clinic. The One-to Zero (OTZ) system which treats the C0-C1 first followed by other spinal regions if clinically indicated, was administered twice weekly until participants reached 80% improvement from baseline symptoms. Shoulder range of motion, peak force and electromyography during maximal resisted scapular elevation (upper trapezius) and neck flexion (sternocleidomastoid), peak grip, and quadricep strength were measured before and after treatment. Repeated measures ANOVAs with pre-planned contrasts (e.g., control to baseline, and post-treatment to baseline) were conducted.</p><p><strong>Results: </strong>Neck and limb control impairments persisted without treatment, with no changes between the double baseline (<i>p</i> > 0.05). Shoulder abduction and extension, and peak force output of the sternocleidomastoid, upper trapezius, and quadriceps improved post-intervention (all <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Selective improvement in neck and limb motor control outcomes post-treatment suggests that increased corticospinal drive/motor neuron excitability from normalized afferent input may impact gross motor output first.</p><p><strong>Clinical registration number: </strong>ACTRN12625000627459. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=389394&isReview=true.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 7","pages":"39548"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Cerebro-Cerebellar Functional Connectivity Associated With Working Memory Decline After Sleep Deprivation.","authors":"Ziyao Wu, Sitong Feng, Sisi Zheng, Linrui Dong, Hongxiao Jia, Yanzhe Ning","doi":"10.31083/JIN36443","DOIUrl":"10.31083/JIN36443","url":null,"abstract":"<p><strong>Background: </strong>It has been demonstrated that the cerebellum plays a critical role not only in motor function but also in cognitive function. Numerous studies have revealed that acute sleep deprivation (SD) alters the functional connectivity (FC) in the cerebral cortex associated with declining working memory (WM). However, the relationship between the altered cerebro-cerebellar FC and white matter damage following acute sleep deprivation remains elusive.</p><p><strong>Methods: </strong>In this study, 26 healthy participants with regular sleep conducted an n-back task and had resting-state functional magnetic resonance imaging (fMRI) scans before and after 24 h of SD. The FC between the cerebrum and cerebellum and its relationship with WM function were analyzed in recruited participants.</p><p><strong>Results: </strong>Our results showed a significantly longer RT for the 1-back and 2-back tasks and lower accuracy of the 2-back task after SD. We found a marked reduction in FC between ten pairs of regions in the cerebellum and cerebrum after SD. Furthermore, a decline in WM performance was positively correlated with the changed FC between the left precentral gyrus and the right lobule X of the cerebellum.</p><p><strong>Conclusion: </strong>Our findings indicate that the impaired FC between the cerebellum and cortical areas may contribute to the decline in WM after acute SD.</p><p><strong>Clinical trial registration: </strong>No: ChiCTR2000039858. Registered 12 November, 2020, https://www.chictr.org.cn/showproj.html?proj=63916.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"36443"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Cerebral Cortical Structural Alterations in Female Patients with Systemic Lupus Erythematosus Without Major Neuropsychiatric Manifestations Accompanied by Anxiety and Depression.","authors":"Zhicheng Liu, Yifan Yang, Shuang Liu, Guofang Zhang, Ru Bai, Shu Li, Ruotong Zhao, Yuqi Cheng, Jian Xu","doi":"10.31083/JIN36382","DOIUrl":"https://doi.org/10.31083/JIN36382","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This study investigated cortical morphological changes in systemic lupus erythematosus (SLE) patients diagnosed with anxiety and/or depression, all of whom exhibited no major neuropsychiatric symptoms and had normal conventional magnetic resonance imaging (MRI) findings. We also further examined the correlation between these morphological alterations and clinical characteristics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Employing advanced structural MRI (sMRI) techniques, we implemented a dual analytical approach combining voxel-based morphometry (VBM) and surface-based morphometry (SBM) to assess structural differences across three cohorts comprising 59 SLE patients with anxiety and/or depression (SLE-AD), 35 SLE patients with no anxiety and/or depression (SLE-NAD), and 48 age-matched healthy controls (HCs). Within the SBM-based analysis framework, we set a minimum clustering threshold of 50 vertices to secure robust outcomes and delineate significant brain regions. The study focused on whole-brain gray matter volume (GMV), cortical thickness (CT), depth of the sulci (SD), cortical gyrification index (GI), and fractal dimension (FD).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Quantitative analyses revealed significant GMV reductions in the SLE-AD group compared with HCs and the SLE-NAD groups (gaussian random field (GRF) correction: &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;voxel&lt;/sub&gt; &lt; 0.0005, &lt;i&gt;p&lt;/i&gt;&lt;sub&gt;cluster&lt;/sub&gt; &lt; 0.0005). Additionally, we observed widespread decreases in the CT and SD, as well as reduced GIs across multiple regions (&lt;i&gt;p&lt;/i&gt;&lt;sub&gt;uncorr&lt;/sub&gt; &lt; 0.001, cluster size &gt;50 vertices). The most prominent alterations were in the left temporal lobe, bilateral thalamus, prefrontal cortex cingulate gyrus, insula, postcentral gyrus, and fusiform gyrus. GMV in the left middle temporal gyrus (&lt;i&gt;r&lt;/i&gt; = -0.288, &lt;i&gt;p&lt;/i&gt; = 0.027) and CT in the left fusiform gyrus (&lt;i&gt;r&lt;/i&gt; = -0.337, &lt;i&gt;p&lt;/i&gt; = 0.009), along with CT in the right middle frontal sulcus (&lt;i&gt;r&lt;/i&gt; = -0.306, &lt;i&gt;p&lt;/i&gt; = 0.018) and right middle frontal gyrus (&lt;i&gt;r&lt;/i&gt; = -0.356, &lt;i&gt;p&lt;/i&gt; = 0.006), were inversely associated with SLE disease activity index (SLEDAI). However, neither GMV, CT, nor cortical complexity exhibited significant associations with Hamilton Anxiety Scale (HAMA) or Hamilton Depression Scale (HAMD) scores. Multivariate linear regression analysis indicated that the CT of left hemisphere-related brain areas-including the superior occipital gyrus, parieto-occipital sulcus, cuneus and opercular part of the inferior frontal gyrus-and the GI of the superior frontal gyrus significantly influenced HAMD/HAMA scores. CT of the left hemisphere's intraparietal sulcus and transverse parietal sulci, along with SD of the right hemisphere's central sulcus, were predictors of HAMA scores.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings demonstrate that SLE patients presenting with anxiety and/or depression exhibit distinct neuroanatomical alterations, even without prominent neuropsychiatri","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"36382"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conical Chitosan Conduits Combined With Methylcobalamin for Sciatic Nerve Transposition Repair.","authors":"Qicheng Li, Fengshi Zhang, Shiyan Liu, Yusong Yuan, Yuhui Kou","doi":"10.31083/JIN36965","DOIUrl":"https://doi.org/10.31083/JIN36965","url":null,"abstract":"<p><strong>Background: </strong>The repair technology of peripheral nerve injuries has made great progress, but the simultaneous repair and promotion of nerve regeneration in multiple distal nerves remains a challenging task. The current cylindrical nerve conduits are unsuitable for nerve transposition repair. This study aims to assess the effect of conical chitosan conduits (different inner diameters at both ends) on nerve transposition repair, in conjunction with methylcobalamin (MeCbl).</p><p><strong>Methods: </strong>In this study, a conical chitosan conduit was used to bridge a 2 mm defect between the proximal common peroneal nerve and distal tibial nerve and common peroneal nerve in rats. Additionally, we administered MeCbl at various concentrations to evaluate post-surgical adjuvant treatment effect. At 16 weeks post-surgery, gait analysis, electrophysiology testing, transmission electron microscopy (TEM) observation, toluidine blue staining, immunofluorescence staining, muscle wet weight determination and Masson's trichrome staining were performed to assess nerve regeneration and reinnervation of gastrocnemius.</p><p><strong>Results: </strong>Gross observations did not reveal the formation of neuromas after bridging the distal nerves in each group. In terms of motor function (**<i>p</i> < 0.01), compound muscle action potential (CMAP) amplitude and latency (**<i>p</i> < 0.01), the quantity of regenerated nerve fibers, muscle fiber morphology and other parameters (**<i>p</i> < 0.01), 200 μg/kg MeCbl administration as a supplementary treatment had a significant positive impact compared to the chitosan conduit+normal saline (Chi/NS) group.</p><p><strong>Conclusions: </strong>Our findings demonstrated that conical chitosan conduits combined with MeCbl can effectively promote nerve transposition repair following multiple distal nerve injuries.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"36965"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Basolateral Amygdalar Cholinergic Neuromodulation in Emotional Learning.","authors":"Victor Manuel Torres-Garcia, Emmanuel Rodriguez-Nava, Gabriel Roldan-Roldan, Donald B Katz, Jean-Pascal Morin","doi":"10.31083/JIN26868","DOIUrl":"https://doi.org/10.31083/JIN26868","url":null,"abstract":"<p><p>The basolateral amygdala (BLA) is crucial for assigning emotional valence to sensory experiences, driving approach or avoidance behaviors during subsequent encounters. Particularly, the BLA plays a critical role in the coding, storage and retrieval of emotional learning. While traditionally viewed through the lens of memory consolidation, cholinergic signaling-mediated by dense inputs from the basal forebrain and abundant muscarinic receptors (mAChRs) in the BLA-plays a far more dynamic role. Acetylcholine, often described as a \"memory molecule\", is central to this process, with scopolamine induced amnesia models underscoring its importance. Recent evidence suggests that cholinergic activity not only supports memory formation but also imparts emotional valence under specific conditions. This review examines the molecular and cellular mechanisms by which mAChR-mediated cholinergic signaling modulates BLA processing and the storage of emotional memories. We integrate psychopharmacological insights with loss and gain-of-function studies to demonstrate how cholinergic signaling in the BLA shapes approach and avoidance behaviors. Based on this evidence, we propose that acetylcholine's influence in the BLA is highly context-dependent, reflecting its versatile role in emotional processing beyond mere memory consolidation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"26868"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Activation of Hippocampal Microglial Cells and Their Role in the Regulation of Pain.","authors":"Lei Chen, Li Zeng, Wu Li, Jiang-Shan Li","doi":"10.31083/JIN27730","DOIUrl":"https://doi.org/10.31083/JIN27730","url":null,"abstract":"<p><p>Chronic pain frequently coexists with adverse emotions, including anxiety and depression, significantly affecting patients' physical and psychological health as well as their quality of life. Changes in hippocampal synaptic architecture, neuronal injury, and diminished neurogenesis significantly contribute to pain-related emotions. Microglia in the hippocampus are implicated in these pathologies. Stimulation or injury leads to microglial activation, which causes pain; prolonged pain causes microglia to continuously release pro-inflammatory factors that induce astrocyte activation, which mediates the apoptosis of hippocampal neurons and abnormal neurogenesis. Concurrently, microglia exhibit aberrant phagocytosis and augmented pruning of hippocampal dendritic spines, which disrupts synaptic plasticity and influences hippocampal long-term potentiation, hence contributing to the emergence of negative emotions. Inflammatory responses in the brain are a prevalent pathological foundation for mood disorders and pain, and the activation or inhibition of microglia M1 polarization can influence pain-related emotions. This review elucidates the significance of hippocampal microglia activation, and their interactions with neurons in the hippocampus and astrocytes, in pain-related emotions.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"27730"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmine-mediated Reduction of Bone Cancer Pain in Rats Correlates With Suppressed DYRK1A/NF-κB Signaling Axis.","authors":"Shuyao Zhang, Shang Zheng, Jia Jin, Yuhua Li, Liping Chen, Junjie Lin, Ming Yao, Longsheng Xu","doi":"10.31083/JIN38100","DOIUrl":"https://doi.org/10.31083/JIN38100","url":null,"abstract":"<p><strong>Background: </strong>Bone cancer pain (BCP) is a prevalent chronic pain condition and a common clinical symptom in patients with advanced cancer. It significantly affects the mobility and quality of life of patients; however, current treatments offer limited efficacy. Harmine, a beta-carboline alkaloid extracted from <i>Peganum harmala</i>, exhibits anti-inflammatory, anxiolytic, analgesic, and neuroprotective properties. However, its antinociceptive properties and mechanisms in BCP models remain unclear. This study aimed to systematically investigate the analgesic effects of Harmine in rats with BCP and explore its underlying molecular mechanisms.</p><p><strong>Methods: </strong>Using databases such as SwissTargetPrediction and Polypharmacology Browser, molecular docking analysis, behavioral tests, and biochemical analysis, we comprehensively evaluated the effects of Harmine in the BCP model.</p><p><strong>Results: </strong>The results demonstrated that Harmine significantly alleviated BCP induced by Luciferin-Malignant Atypical Discrete Breast 106 cells (LUC-MADB106) in a dose-dependent manner. Intrathecal administration of Harmine significantly inhibited the upregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) expression and the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in the spinal cord dorsal horn (SCDH) of rats with bone cancer.</p><p><strong>Conclusions: </strong>These findings suggest that Harmine has significant therapeutic potential for alleviating BCP hyperalgesia, providing a foundation for the future development of new drugs targeting BCP.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"38100"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging Effects on Absolute and Relative Estrogen Receptor Variant Gene Expression Levels in Male Versus Female Rat Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neurons.","authors":"Rami Shrestha, Subash Sapkota, Karen P Briski","doi":"10.31083/JIN38142","DOIUrl":"10.31083/JIN38142","url":null,"abstract":"<p><strong>Background: </strong>Aging alters estrogen receptor (ER) expression in distinctive hypothalamic loci, but information regarding potential adjustments in estradiol receptivity at the individual neuron population level remains incomplete. Estradiol controls glucostasis by action on ventromedial hypothalamic nucleus (VMN) targets. VMN growth hormone-releasing hormone (Ghrh) neurons exhibit sex-dimorphic ER variant and counterregulatory transmitter gene profiles in young adult rats.</p><p><strong>Methods: </strong>Combinatory single-cell laser-catapult-microdissection/multiplex qPCR analyses was used to investigate whether aging changes nuclear versus cytoplasmic <i>ER</i> gene expression according to sex.</p><p><strong>Results: </strong>Ghrh neuron <i>ER-alpha</i> and G-protein-coupled estrogen receptor-1 (<i>GPER</i>) transcription was decreased in old versus young rats of each sex. Old animals lacked ER-alpha transcriptional reactivity to hypoglycemia, indicative of age-associated loss of response. Hypoglycemia had divergent effects on <i>ER-beta</i> transcription, with no effect found in old males versus an inhibitory effect in old female rats. Hypoglycemic inhibition of Ghrh neuron <i>GPER</i> gene expression in old male and female rats was similar to that which occurred in corresponding young animals. <i>Ghrh</i> gene silencing identified age-related loss of neuropeptide modulatory regulation of <i>ER</i> gene transcription. <i>Ghrh</i> signaling inhibited eu- and hypoglycemic Ghrh neuron <i>aromatase</i>/<i>CYP19A1</i> mRNA profiles in old male and female rats; in each sex, this gene transcript was refractory to hypoglycemia regardless of age.</p><p><strong>Conclusions: </strong>VMN Ghrh neuron neuroestradiol production may be up-regulated with age, but cellular sensitivity to this local steroid signal may differ between young and old rats due to differences in ER variant expression. Further research is warranted to examine how potential age-associated modifications in absolute and proportionate signaling by distinctive ER may affect Ghrh neuron glucose-regulatory neurotransmission in male versus female rats.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"38142"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560350","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}