IBRO Neuroscience Reports最新文献

{"title":"Obesity-induced cofilin1 pathway dysregulation: Possible molecular links between neuroinflammation, cognitive decline, and Alzheimer's disease biomarkers","authors":"Amsha S. Alsegiani ,&nbsp;Bdour Alshalawi,&nbsp;Shaden Alzahrani,&nbsp;Nourah Z. Alzoman,&nbsp;Aliyah Almomen","doi":"10.1016/j.ibneur.2025.10.001","DOIUrl":"10.1016/j.ibneur.2025.10.001","url":null,"abstract":"<div><div>Obesity is a growing concern globally, particularly among young populations. Cofilin1, a major actin-depolymerizing factor (ADF) isoform in the CNS, acts as a stress protein that triggers neuroinflammation and correlates with the onset of Alzheimer's disease (AD). However, its role in obesity has not yet been identified. In this study, we investigated the influence of diet-induced obesity on cofilin1 dysregulation in the brain and its correlation to neurobehavioral deficiencies, neuroinflammation, synaptic dysfunction, and AD biomarkers. Male C57BL/6 mice were fed a regular diet (control) or a high-fat diet (HFD, obese) for 7 weeks to induce obesity. Our data demonstrate that the activation of cofilin1 in the hippocampus region of HFD mice brains is mediated by Slingshot homolog-1 (SSH1) overactivation and LIM kinase-1 (LIMK1) inactivation. However, pcofilin1 is also increased, but this increase might be mediated by mechanisms other than an actin-dependent mechanism. Cofilin1 pathway dysregulation in HFD-fed mice was correlated with cognitive decline, as assessed using the Morris water maze (MWM) and Y-maze, and increased astrocytic activation protein and synaptotoxicity by downregulating pre- and post-synaptic markers. It also correlates with the significant upregulation of AD biomarkers (pTau_Ser396) in the brain, saliva, and serum. At the systemic level, our results showed dysregulation of the gut microbiota, characterized by a ∼53 % increase in the Firmicutes: Bacteroidetes ratio in HFD-fed mice. HFD-fed mice also exhibited a significant increase in certain inflammatory and anti-inflammatory blood cytokines. Our findings suggest that active cofilin1 plays a significant role in diet-induced obesity and may become a potential therapeutic target.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 699-708"},"PeriodicalIF":2.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Napping restores working memory and brain activation impaired by sleep deprivation","authors":"Anping Ouyang ,&nbsp;Jun Jiang ,&nbsp;Lin Wu ,&nbsp;Xinxin Lin ,&nbsp;Lingling Wang ,&nbsp;Qiutao Yan ,&nbsp;Xuqian Diao ,&nbsp;Yan Li ,&nbsp;Yuanqiang Zhu ,&nbsp;Lingli Zeng ,&nbsp;Jiaxi Peng ,&nbsp;Qianqian Dong ,&nbsp;Wei He ,&nbsp;Peng Fang","doi":"10.1016/j.ibneur.2025.09.013","DOIUrl":"10.1016/j.ibneur.2025.09.013","url":null,"abstract":"<div><h3>Background</h3><div>Sleep deprivation (SD) impairs working memory (WM), yet the restorative potential of brief daytime naps remains underexplored. This study examines how naps counteract SD-induced WM deficits through behavioral and neuroimaging mechanisms, focusing on task-positive networks and default mode network (DMN) dynamics.</div></div><div><h3>Method</h3><div>A within-subject fMRI study employed 2-back WM tasks in 50 participants under three conditions: baseline wakefulness, post-30h SD, and post-nap recovery. Behavioral metrics (reaction times, accuracy) and fMRI activation patterns were analyzed using repeated-measures ANOVA and mixed-effects models to assess SD and nap effects.</div></div><div><h3>Result</h3><div>Naps partially restored SD-induced WM declines, improving reaction times and accuracy. Post-SD, reduced activation in the cerebellum, insula, and thalamus (attention/executive regions) rebounded post-nap. SD weakened DMN suppression (middle frontal gyrus, precuneus, superior temporal gyrus), with maximal DMN suppression post-nap. Improved WM performance correlated with reactivated task-positive networks.</div></div><div><h3>Conclusion</h3><div>Daytime naps mitigate SD-related WM deficits by rebalancing task-positive network activation (cerebellum, thalamus) and enhancing DMN suppression. These findings elucidate neurophysiological mechanisms of sleep-cognition interactions, supporting naps as a practical intervention for SD-induced cognitive impairment</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 709-717"},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospero-related homeobox protein 1 (Prox1) enhances myelin sheath regeneration in injured sciatic nerve","authors":"Linlin Jie,&nbsp;Xuening Jing,&nbsp;Jie Liu,&nbsp;Jun Ren,&nbsp;Xiaoni Kong,&nbsp;Jun Wu,&nbsp;Fanwei Meng","doi":"10.1016/j.ibneur.2025.09.011","DOIUrl":"10.1016/j.ibneur.2025.09.011","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral nerve injury (PNI), such as sciatic nerve injury (SNI), often results in poor functional recovery due to myelin damage, which critically impairs nerve regeneration. Prox1, a homeobox transcription factor known to influence neurogenesis, has not been studied in peripheral myelin regeneration.</div></div><div><h3>Objective</h3><div>To investigate morphological changes in myelin sheaths and the expression of Prox1 and MBP proteins during sciatic nerve repair, and to determine the role of Prox1 in nerve regeneration.</div></div><div><h3>Methods</h3><div>Mice were divided into seven groups (n = 8): one control and six experimental groups based on sciatic nerve collection at Days 3, 4, 5, 6, 7, and 14 post-injury. H&amp;E staining, electron microscopy, Luxol Fast Blue staining, Western Blot, and immunohistochemistry were used to assess myelin morphology and Prox1/MBP expression. Immunofluorescence analyzed colocalization of Prox1 and MBP. Prox1 was overexpressed in Schwann cells via plasmid transfection, and MBP levels were measured by Western blot.</div></div><div><h3>Results</h3><div>Control group myelin sheaths showed normal structure, while Day 7 nerves displayed disorganized sheaths with vacuolation and axonal spacing. By Day 14, myelin structure largely recovered. MBP levels decreased from Day 3, reached a minimum at Day 7, and increased significantly by Day 14. Prox1 expression rose on Day 3, peaked on Day 7, and declined by Day 14. Prox1 and MBP colocalized in injured nerves, and Prox1 overexpression significantly increased MBP levels in Schwann cells.</div></div><div><h3>Conclusion</h3><div>Prox1 protein level is upregulated in injured sciatic nerve, and Prox1 overexpression promotes the increase of MBP protein level, which positively correlates to myelin regeneration in morphology. This strongly suggests that Prox1 promotes myelin regeneration of injured peripheral nerves.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 679-687"},"PeriodicalIF":2.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond apoptosis: Exploring necroptosis, ferroptosis, and pyroptosis in sevoflurane- and isoflurane-associated PNDs","authors":"Haiyan Sun ,&nbsp;Rong Cai ,&nbsp;Minjuan Zhao ,&nbsp;Yisi Shan ,&nbsp;Ke Ma ,&nbsp;Min Qian","doi":"10.1016/j.ibneur.2025.09.012","DOIUrl":"10.1016/j.ibneur.2025.09.012","url":null,"abstract":"<div><div>Perioperative neurocognitive disorders (PNDs) are common postoperative complications, particularly in elderly patients undergoing general anesthesia. While sevoflurane and isoflurane are widely used inhalational anesthetics, their association with PNDs requires deeper mechanistic investigation. Although apoptosis was traditionally considered the primary mechanism, recent evidence implicates non-apoptotic programmed cell death (PCD) pathways-necroptosis, ferroptosis, and pyroptosis-in PND pathogenesis. These pathways amplify neuroinflammation and neuronal damage through distinct molecular mechanisms. This review synthesizes current understanding of these PCD pathways in inhalational anesthetic-induced neurotoxicity, evaluating their molecular signatures and interactions. We identify critical knowledge gaps and propose research directions focusing on pathway dominance, crosstalk, and multi-target therapeutic strategies. These insights advance PND pathophysiology understanding and inform novel treatment development.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 688-698"},"PeriodicalIF":2.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAB receptor-mediated potentiation of ventral medial habenula glutamatergic transmission in GABAergic and glutamatergic interpeduncular nucleus neurons","authors":"Hannah E. Stinson,&nbsp;Ipe Ninan","doi":"10.1016/j.ibneur.2025.09.010","DOIUrl":"10.1016/j.ibneur.2025.09.010","url":null,"abstract":"<div><div>The medial habenula (MHb)-interpeduncular nucleus (IPN) pathway plays a crucial role in information transferring between the forebrain and the midbrain, and has been implicated in the regulation of fear behavior and nicotine addiction. The synapses between the ventral MHb and the IPN show a unique property, i.e., an enhancement of synaptic transmission upon activation of GABA_B receptors. Although IPN is known to contain parvalbumin (PV) and somatostatin (SST) GABAergic neurons and vesicular glutamate transporter 3 (VGLUT3)-expressing neurons, it is unknown how GABA_B receptor activation affects ventral MHb-mediated glutamatergic transmission onto these three subtypes of IPN neurons. Our studies show robust glutamatergic connectivity from ventral MHb to PV and SST neurons in the IPN, while the ventral MHb-mediated glutamatergic transmission in IPN VGLUT3 neurons is weak. Activation of GABA_B receptors produces a robust potentiation of ventral MHb-mediated glutamatergic transmission in PV neurons, while a modest effect was observed in IPN SST neurons. In addition, activation of GABA_B receptors causes transient conversion of non-responding ventral MHb synapses into active synapses in some IPN VGLUT3 neurons. Thus, our results demonstrate that GABA_B receptor activation produces a differential effect on ventral MHb-mediated glutamatergic transmission onto PV, SST, and VGLUT3 neurons in the IPN.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 655-660"},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption","authors":"Jing Yang ,&nbsp;Ning Tang ,&nbsp;Ruanxian Dai ,&nbsp;Jiajie Chen ,&nbsp;Zhaojiao Li ,&nbsp;Fengwen Jiang ,&nbsp;Shiyi Li ,&nbsp;Qiang Meng","doi":"10.1016/j.ibneur.2025.09.008","DOIUrl":"10.1016/j.ibneur.2025.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Proteoglycan 4 (PRG4) possesses biological characteristics of anti-inflammation, lubrication, anti-apoptosis, and immunomodulation, and regulates the homeostasis of articular cartilage, myocardium, brain, and skin tissues. Nevertheless, the function of PRG4 in post-stroke hemorrhagic transformation (HT) and blood-brain barrier (BBB) disruption is unknown.</div></div><div><h3>Methods</h3><div>A post-stroke HT mouse model (MACO-HT) was constructed and subsequently treated with recombinant PRG4 by tail vein injection. Neurologic impairment in mice was evaluated using mNSS and Zea longa score. The effect of recombinant PRG4 on HT was assessed using HE and TTC staining and hemoglobin assays. The effect of recombinant PRG4 on BBB repair was evaluated using Evan's blue leakage, western blotting, and IF staining assays.</div></div><div><h3>Results</h3><div>Recombinant PRG4 reduced mNSS and Zea longa scores in MACO-HT mice. Infarct and hemorrhage areas and hemoglobin level in brain tissues of MACO-HT mice were significantly diminished after treatment with recombinant PRG4. MACO-HT mice exhibited significant Evan's blue leakage, which was ameliorated by reconstituted PRG4. Moreover, recombinant PRG4 notably diminished the levels of TLR2, MMP-2, and MMP-9 proteins, and augmented the levels of Claudin-5, Occludin, and ZO-1 in the brain tissues of MACO-HT mice.</div></div><div><h3>Conclusion</h3><div>Recombinant PRG4 ameliorated post-stroke neurological impairment, HT, and BBB disruption. This finding identifies a biological function for PRG4 in stroke and provides support for therapeutic strategies targeting HT and BBB injury.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 661-667"},"PeriodicalIF":2.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different mechanisms of axitinib and diazepam antiseizure action in pentylenetetrazol-induced kindling model","authors":"Leonid S. Godlevsky ,&nbsp;Işınsu Alkan ,&nbsp;Kıymet Kübra Tüfekci ,&nbsp;Mykhailo P. Pervak ,&nbsp;Süleyman Kaplan","doi":"10.1016/j.ibneur.2025.09.005","DOIUrl":"10.1016/j.ibneur.2025.09.005","url":null,"abstract":"<div><h3>Introduction</h3><div>This study intended to assess the histomorphology characteristics of hippocampal structures and determine the severity of seizures after treatment with the tyrosine kinase B inhibitor axitinib and diazepam in fully developed and postponed period in PTZ-kindled rats.</div></div><div><h3>Methods and materials</h3><div>Wistar rats were given PTZ for 21 days until fully developed convulsions were achieved. Two protocols were explored: assessment of seizures immediately after the completion of the kindling (early kindling) and after a two-week post-kindling PTZ-free period. Treatment with axitinib and diazepam was performed before early and postponed kindling seizures assessment, with the consequent collection of brains for histomorphology.</div></div><div><h3>Results</h3><div>Axitinib and diazepam effectively reduced seizure severity at the early and postponed periods of kindling. Axitinib's antiseizure effectiveness was reduced in the postponed stage of kindling period compared with the early one (P = 0.039), while diazepam's effectiveness was maintained at a similar level (P &gt; 0.05). Stereological quantification of neuronal hippocampus changes revealed an increase in the total volume of the stratum radiatum, while a decrease of the dentate gyrus, in postponed compared with early kindling (P &lt; 0.05). The positivity of collagen type IV, which is present in the blood-brain barrier, increased and was more pronounced in the postponed period in hippocampal structures (CA1-CA3).</div></div><div><h3>Conclusion</h3><div>The antiseizure effect of tyrosine kinase B inhibition with a specific antagonist of VEGF axitinib is particularly pronounced in the early phase of PTZ kindling. Opposite to axitinib, diazepam demonstrated a similar antiseizure action in both periods of kindling. These results suggest a more pronounced contribution of angiogenesis compared with the neuronal degenerative hippocampal damage to the development of PTZ-kindled chronic epileptogenesis.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 668-678"},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disorganized hippocampal excitatory and inhibitory connectivity in a mouse model of Alzheimer’s disease","authors":"Tetsufumi Ito ,&nbsp;Munenori Ono ,&nbsp;Sachiko Yamaki ,&nbsp;Yoshie Hori ,&nbsp;Shinji Muramoto ,&nbsp;Ryo Yamamoto ,&nbsp;Takafumi Furuyama ,&nbsp;Nobuo Kato","doi":"10.1016/j.ibneur.2025.09.004","DOIUrl":"10.1016/j.ibneur.2025.09.004","url":null,"abstract":"<div><div>Cortical hyperexcitability is regarded to accompany Alzheimer’s disease (AD) and its rodent models, and often claimed to be even causative of AD. To seek its morphological backgrounds, spatial learning was assessed with the Morris water maze test (MWM) in male 3xTg Alzheimer’s model mice of 5–6 months old, then their hippocampal tissue was examined by electron microscopy (EM). By assigning EM-based asymmetric and symmetric synapses to excitatory (E) and inhibitory (I) synapses, respectively, and by attributing synapses on spines to those onto excitatory (E) postsynaptic neurons, we defined 2 different types of synapses: E-to-E and I-to-E synapses. In addition, synapses onto non-spinous structures (N) of postsynaptic neurons were designated as E-to-N or I-to-N. We thus categorized hippocampal synapses into 4 classes. I-to-E synapses were 7-fold denser in 3xTg than in wild-type mice, whereas the other types did not differ in density. In MWM, there was a non-significant tendency that AD mice perform worse than WT mice. We found a non-significant tendency for the E-to-E synapse density to correlate inversely with MWM performance in AD mice, though the correlation was significant with AD and WT mice pooled together. When E-to-E and E-to-N synapses are combined as the asymmetric synapse class, the density was significantly correlated in AD mice isolated. The I-to-E synapse density in AD mice exhibited the tendency to inverse correlation with MWM performance. Overall, categorizing hippocampal synapses into 4 classes, we confirmed from a new angle the received view that a higher hippocampal excitability could deteriorate cognition.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 646-654"},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asia-Pacific perspectives in neuroscience: Insights from the IBRO APRC mini-series","authors":"Huong Thi Thanh Ha","doi":"10.1016/j.ibneur.2025.09.003","DOIUrl":"10.1016/j.ibneur.2025.09.003","url":null,"abstract":"","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Page 645"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of ventromedial hypothalamic nucleus growth hormone-releasing hormone neuron counterregulatory neurochemical marker gene expression in young adult versus middle-aged male and female rats","authors":"Rami Shrestha,&nbsp;Subash Sapkota,&nbsp;Karen P. Briski","doi":"10.1016/j.ibneur.2025.09.002","DOIUrl":"10.1016/j.ibneur.2025.09.002","url":null,"abstract":"<div><div>Aging impairs glucose counterregulatory function by unknown mechanisms. Ventromedial hypothalamic nucleus/dorsomedial division (VMNdm) growth hormone-releasing hormone (Ghrh) neurons control counterregulation through Ghrh-modulated discharge of structurally diverse co-expressed neurochemicals. Current research used gene silencing and single-cell laser-catapult-microdissection/multiplex qPCR tools to investigate whether aging alters eu- and/or hypoglycemic patterns of co-produced counterregulatory-inhibiting (γ-aminobutyric acid) or -stimulating (Ghrh; glutamate; nitric oxide) neurotransmitter marker genes in this cell population. Data document basal Ghrh mRNA diminution in older, i.e., middle-aged rats of each sex and age-specific Ghrh transcriptional responses to hypoglycemia in females. Older rats showed Ghrh repression of glutamate decarboxylase₆₇ (GAD₆₇) and GAD₆₅ mRNAs, a gain of inhibitory tone in female. In middle-age male rats, both GAD transcripts were refractory to hypoglycemia, an age-related response loss. In older females, hypoglycemia stimulated GAD₆₅ gene expression, contrary to Ghrh-mediated repression in young adult animals. Ghrh suppressed glutaminase (GLS) mRNA in middle-aged rats of each sex, like young adults. Unlike young adult males, older males showed no GLS transcriptional response to hypoglycemia; older hypoglycemic females exhibited up-regulated GLS mRNA, differing from down-regulated expression in younger animals. Aging reduced neuronal nitric oxide synthase (nNOS) gene profiles in females only; nNOS transcription was increased by hypoglycemia in middle-aged rats irrespective of sex, but was unopposed by Ghrh, indicating loss of this inhibitory tone. Results bolster the notion that by midde-age, aging may adjust, according to sex, multi-modal transmitter signaling by VMNdm Ghrh neurons to the brain glucose-regulatory network. Further research is justified to ascertain consequences of aging-associated patterns of co-expressed transmitter release on counterregulation in each sex.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 632-644"},"PeriodicalIF":2.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}