Neuroscience最新文献

{"title":"Study on resting-state brain network alterations in flight trainees based on independent component analysis","authors":"Lu Ye ,&nbsp;Liya Ba ,&nbsp;Haiqing Si ,&nbsp;Dongfeng Yan","doi":"10.1016/j.neuroscience.2025.05.305","DOIUrl":"10.1016/j.neuroscience.2025.05.305","url":null,"abstract":"<div><div>This study aimed to investigate the functional alterations in the resting-state brain networks of flight trainees using the independent component analysis (ICA) method. A total of 33 flight trainees and 33 general college students were recruited. Resting-state fMRI data were collected using a 3.0 T MRI scanner. ICA was employed to extract resting-state brain network components, followed by statistical analyses. Fourteen physiologically independent components were identified during the ICA process and classified into nine networks. The flight trainees exhibited significantly increased activation in the right calcarine fissure within the ventral attention network (FWE corrected, P &lt; 0.05). Moreover, the region of interest values of the differential brain region in flight trainees showed a significant positive correlation with the correct rate of the Berg Card Sorting Test (BCST) and a significant negative correlation with the BCST perseverative error (P &lt; 0.05 for both). The significant activation of the right calcarine fissure of flight trainees may be associated with the high attentional demands of flight tasks. Flight trainees demonstrated superior executive function and attention allocation abilities, providing evidence of adaptive functional adjustments in the brain caused by professional activities.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 157-164"},"PeriodicalIF":2.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired persistence of cortical sensory adaptation following repetitive tactile stimulation in the hindlimb somatosensory cortex of Rett syndrome mice","authors":"Farnoosh Farhoomand,&nbsp;Taylor Kaban,&nbsp;Vasil Kecheliev,&nbsp;Kerry R. Delaney","doi":"10.1016/j.neuroscience.2025.05.304","DOIUrl":"10.1016/j.neuroscience.2025.05.304","url":null,"abstract":"<div><div>Reduced response to repeated stimulation (RS) is a signature feature of sensory systems. In this study we examined cortical sensory responses to brief tactile stimulation of the foot/ankle before, during and after periods of RS in young male, young and old female mice. We compared cortical activity in wild-type (WT) mice to mice with mutation in <em>Mecp2</em> that causes the neurodevelopmental disorder Rett syndrome (RTT). Intrinsic optical signal imaging (IOS) and intracortical local field potential (LFP) measurements revealed reduced cortical responses to test stimuli on the order of 40–50% after 15-min periods of RS. The time-course and magnitude of reduced IOS and LFP to tactile test-stimuli were similar in WT and RTT mice before and during application of RS. However, after cessation of RS, cortical responses remained persistently below pre-stimulation in WT while RTT mice had significantly more rapid and in some cases complete recovery with an hour of rest. LFP responses to each stimulus in a 7-stimulus test-train characteristically decline. Examining the buildup of this adaptation during test-trains revealed that while the response to the first stimulus in the test-train was generally consistent, responses to successive stimuli in the test-train declined more rapidly after application of RS. This increased adaptation during test-trains persisted in WT mice and reversed more rapidly in RTT mice suggesting that persistent cortical sensory adaptation results from enhancement of processes responsible for short-term adaptation. The lack of persistent cortical sensory adaptation in RTT mice may reflect reduced long-term plasticity within central somatosensory processing circuits.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 165-178"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalamic free water elevation and its association with glymphatic dysfunction in Parkinson’s disease: A cross-sectional and longitudinal study","authors":"Zhanyu Kuang ,&nbsp;Xiaofei Huang ,&nbsp;Mengfan Wang ,&nbsp;Shuwen Bu ,&nbsp;Riyu Guo ,&nbsp;Yongzhou Xu ,&nbsp;Amei Chen ,&nbsp;Xinhua Wei","doi":"10.1016/j.neuroscience.2025.05.303","DOIUrl":"10.1016/j.neuroscience.2025.05.303","url":null,"abstract":"<div><div>Free Water (FW) is considered an indicator of neuroinflammation, while the Index of Diffusivity along the Perivascular Space (ALPS) is a recently introduced measure of glymphatic function. However, no study has yet investigated the specific relationships between these factors simultaneously. This study aimed to examine changes in FW in the thalamic midline and lateral nuclei in Parkinson’s disease (PD), with a particular focus on the potential influence of glymphatic system dysfunction. MRI data and clinical information were obtained from 32 healthy controls (HC), 32 participants with prodromal PD (pPD), and 90 participants with PD, sourced from the Parkinson’s Progression Markers Initiative (PPMI) database. The ALPS index and Free Water fractional volume (FWF) were calculated based on diffusion tensor images. Intergroup comparisons of and correlations among MRI measures and clinical assessments were analyzed. FWF was elevated in the bilateral thalamic midline and right lateral nuclei of PD and in right midline nuclei of pPD compared to HC. In the PD group, the right ALPS index was significantly and negatively associated with FWF in the bilateral thalamic lateral nuclei, and mean ALPS index was negatively correlated to FWF in right lateral nuclei. Moreover, FWF in the right lateral thalamic nuclei of PD was correlated with follow-up Montreal Cognitive Assessment (MoCA) scores and its 2-years decrease rate. We provided indirect evidence to support that thalamic FW was significantly increased in PD participants, potentially exacerbated by glymphatic system dysfunction.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 218-226"},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the combined neuroprotective effects of resveratrol and hesperidin in a scopolamine-induced rat model of cognitive impairment","authors":"Bedanta Bhattacharjee ,&nbsp;Anshul Shakya ,&nbsp;Naveen Shivavedi ,&nbsp;Ram Kumar Sahu ,&nbsp;K. Sandhanam","doi":"10.1016/j.neuroscience.2025.05.302","DOIUrl":"10.1016/j.neuroscience.2025.05.302","url":null,"abstract":"<div><div>The occurrence of cognitive impairment in normal aging and sporadic Alzheimer’s disease is linked to oxidative stress. Resveratrol, a polyphenolic molecule, and hesperidin, a flavanone glycoside have exhibited powerful anti-oxidant and neuroprotective effects. The present study was designed to explore the neurotherapeutic potential of combination between resveratrol and hesperidin as preventative herbal remedies to inhibit oxidative stress and cholinergic and mitochondrial dysfunction in scopolamine-induced cognitive impairments in rats. Resveratrol (20 mg/kg, <em>p.o.</em>), hesperidin (20 mg/kg, <em>p.o.</em>), and its combination were administered orally up to 21 days. Cognitive impairment was induced by intraperitoneal injection of scopolamine (1 mg/kg, <em>i.p.</em>) to rats for 5 days (15th, 16th, 17th, 18th, and 19th). Learning and memory function in rats were appraised by using the Morris water maze. Subsequently, the content of oxidative-nitrosative stress parameters, the activity of acetylcholinesterase (AChE), electron transport chain complexes, brain-derived neurotrophic factor (BDNF), and pro-inflammatory cytokines mediators (TNF-α and IL-6) in hippocampus brain areas of rats were measured. Scopolamine treatment significantly produced learning and memory impairment, oxidative-nitrosative stress, cholinergic dysfunction, mitochondrial deficit, reduced BDNF, and increased TNF-α and IL-6 levels. Whereas, resveratrol and hesperidin combination therapy effectively improved brain anti-oxidant status, lowered brain mitochondrial impairments, and neuro-inflammation in rats as compared to mono-therapy. Our findings demonstrated that the resveratrol and hesperidin combination group showed excellent anti-cognitive impairment properties compared to single therapy. The combination therapy exhibited a favorable effect in suppressing scopolamine-induced cognitive impairment, either additively, synergistically, or through distinct molecular pathways.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 54-68"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis reveals potential targets associated with hippocampus vulnerability in spatial cognitive dysfunction of type 2 diabetes mellitus rats","authors":"Ying Zhang ,&nbsp;Dongmei Su ,&nbsp;Yuru Liu ,&nbsp;Bin He ,&nbsp;Huiping Wang ,&nbsp;Cuige Shi ,&nbsp;Yishu Yang","doi":"10.1016/j.neuroscience.2025.05.036","DOIUrl":"10.1016/j.neuroscience.2025.05.036","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive dysfunction is one of the major complications of T2DM.<!--> <!-->However, the precise molecular mechanism underlying this relationship remains unclear. Present study aimed to identify potential predictors of cognitive dysfunction associated with T2DM specifically within the hippocampus.</div></div><div><h3>Methods</h3><div>T2DM was induced by a high-fat diet combined with streptozotocin injections. Morris water maze was employed to assess spatial cognitive ability. HE staining was used to evaluate neurons injury in hippocampus. Transcriptome sequencing was conducted on the hippocampus to identify potential genes. The results obtained from sequencing analysis were<!--> <!-->validated using qRT-PCR. GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways.</div></div><div><h3>Results</h3><div>Compared with CON rats, the<!--> <!-->spatial cognitive ability decreased in T2DM rats. Hippocampus neurons reduced in CA1 area of T2DM rats. In total, 123 DEGs<!--> <!-->were identified by<!--> <!-->transcriptome sequencing, including 25 upregulated genes and 98 downregulated genes. The qRT-PCR results verified the RNA-seq. KEGG pathway analysis showed the major enriched pathways were TNF signaling pathway, arachidonic acid metabolism, AGE-RAGE signaling pathway in diabetic complications, and cellular senescence. GO analysis showed that DEGs involved in biological process were mainly related to vasculogenesis, response to hypoxia, regulation of cell proliferation and aging.</div></div><div><h3>Conclusions</h3><div>Our transcriptomic analysis reveals the “cellular senescence” signaling pathway may be implicated in T2DM-induced spatial cognitive dysfunction and Tgfbr2 may be the important DEG involved in this pathway, which will be the primary focus of our future research endeavors.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 35-46"},"PeriodicalIF":2.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Task-related reconfiguration patterns of frontoparietal network during motor imagery","authors":"Long Chen ,&nbsp;Lei Zhang ,&nbsp;Zhongpeng Wang ,&nbsp;Qi Li ,&nbsp;Bin Gu ,&nbsp;Dong Ming","doi":"10.1016/j.neuroscience.2025.05.035","DOIUrl":"10.1016/j.neuroscience.2025.05.035","url":null,"abstract":"<div><div>Motor imagery (MI) is closely associated with the frontoparietal network that includes prefrontal and posterior parietal regions. Studying task-related network reconfiguration after brain shifts from the resting state to the MI task is an important way to understand the brain’s response process. However, how the brain modulates functional connectivity of the frontoparietal network when it shifts to MI has not been thoroughly studied. In this study, we attempted to characterize the frontoparietal network reconfiguration patterns as the brain transitioned to motor imagery tasks. We performed the analysis using EEG signals from 52 healthy subjects during left- and right-hand MI tasks. The results indicated distinct reconfiguration patterns in the frontoparietal network across four typical brain wave rhythms (theta (4 ∼ 7 Hz), alpha (8 ∼ 13 Hz), beta (14 ∼ 30 Hz), and gamma (31 ∼ 45 Hz)). Meanwhile, there was a significant positive correlation between the frontoparietal network reconfiguration and the event-related desynchronization of alpha and beta rhythms in the sensorimotor cortex. We further found that subjects with better MI-BCI performance exhibited greater reconfiguration of the frontoparietal network in alpha and beta rhythms. These findings implied that MI was accompanied by a shift in information interaction between brain regions, which might contribute to understanding the neural mechanisms of MI.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 302-311"},"PeriodicalIF":2.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics analysis reveals immunovascular mechanisms of the placenta-maternal brain axis and lifespan neurobehavior changes in a mouse model of preeclampsia","authors":"Serena Gumusoglu ,&nbsp;Brianna Blaine ,&nbsp;Aimee Bertolli ,&nbsp;Matthew A. Weber ,&nbsp;Mushroor Kamal ,&nbsp;Hannah Hazzard ,&nbsp;Brandon Schickling ,&nbsp;Marisol Lauffer ,&nbsp;Yuping Zhang ,&nbsp;Robert Taylor ,&nbsp;Keagan Kirkpatrick ,&nbsp;Donna Santillan ,&nbsp;Georgina Aldridge ,&nbsp;Mark Santillan","doi":"10.1016/j.neuroscience.2025.05.301","DOIUrl":"10.1016/j.neuroscience.2025.05.301","url":null,"abstract":"<div><div>Preeclampsia (PE) is a hypertensive disorder of pregnancy, among the leading global drivers of maternal morbidity. PE can precipitate neuropsychiatric risk, including for peripartum anxiety, depression, and cognitive problems. To investigate mechanisms underlying psycho-obstetric risk in PE, we examined maternal metabolic, placental, brain, and behavioral changes in our chronic vasopressin (AVP) infusion PE mouse model (C57Bl6/J). Elevated maternal AVP secretion predicts PE in humans, and chronic AVP administration is sufficient to phenocopy immune, obstetric, and renal phenotypes of PE in pregnant mice. Late-pregnancy metabolomics (N = 4–6/condition/tissue) revealed no significant disruptions in plasma, but 33 changed metabolites were changed in AVP mouse placenta, implicating altered protein, energy, and nutrient functions. Placental RNA sequencing (RNA-seq; N = 3/condition) revealed 140 differentially expressed genes (DEGs), with pathway analyses highlighting changes in structural and metabolic remodeling. Placental multi-omic integration (RNA-seq and metabolomics) identified altered purine metabolism. Analysis of RNA-seq-predicted placental secretome suggested altered immunovascular factors (e.g., C2CD4, KLK1B1). In late-gestation maternal brain, RNA-seq (N = 3/condition) revealed extensive gene suppression in the hypothalamic paraventricular nucleus (PVN, 329 DEGs; 322 down-regulated) and frontal cortex (114 DEGs; 113 down-regulated), implicating altered signaling and immune-vascular pathways, respectively. AVP increased antepartum exploratory behavior without changing depressive-like or hedonic behaviors. Spatial memory deficits in aged postpartum AVP dams were also significant and associated with molecular changes in the hippocampus. Overall, the AVP model of PE induces placental and maternal brain changes, invoking immune and vascular mechanisms. This work identifies potential mechanisms underlying PE impacts on maternal brain, with implications for associated mental health challenges.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 69-84"},"PeriodicalIF":2.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capturing dynamic neuronal responses to dominant and subordinate social hierarchy members with catFISH","authors":"Madeleine F. Dwortz ,&nbsp;James P. Curley","doi":"10.1016/j.neuroscience.2025.05.025","DOIUrl":"10.1016/j.neuroscience.2025.05.025","url":null,"abstract":"<div><div>Dominance hierarchies are key to social organization in group-living species, requiring individuals to recognize their own and others’ ranks. This is particularly complex for mid-ranking animals, who navigate interactions with higher- and lower-ranking individuals. Using in situ hybridization, we examined how mid-ranked mice’s brains respond to dominant and subordinate stimuli by labeling activity-induced immediate early genes and neuronal markers. We show that distinct neuronal populations in the amygdala and hippocampus respond differentially across social contexts. In the basolateral amygdala and dorsal endopiriform, glutamatergic <em>Slc17a7</em>⁺ neurons, particularly dopamine-receptive <em>Slc17a7</em>⁺<em>Drd1</em>⁺ neurons, show elevated IEG expression in response to social stimuli, with a higher response to dominant over subordinate animals. Similar response patterns are observed among GABAergic <em>Slc32a1</em>⁺<em>Oxtr</em>⁺ neurons in the medial amygdala. We also identified distinct neural ensembles selectively active in response to dominant and subordinate animals by examining cell reactivation over repeated stimulus presentations. We find a higher degree of reactivation among <em>Slc17a7⁺Oxtr⁺</em> ensembles in the endopiriform when the same individual was presented twice in succession. A similar pattern was observed among <em>Oxtr</em>⁺ neurons in the dentate gyrus hilus, while the inverse was observed among <em>Slc17a7</em>⁺<em>Avrp1b</em>⁺<em>Oxtr</em>⁺ neurons in distal CA2CA3, suggesting distinct encoding or recollection mechanisms across hippocampal subregions. We also highlight methodological advances showing that IEG responses are shaped by stimulus duration and the identity of the IEG and timepoint at which expression is measured. This work lays the foundation for further precise, cell type–resolved investigation into how the brain processes social information.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 105-119"},"PeriodicalIF":2.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of emotional processing from cumulative repetitive subconcussion: Evidence from event-related potentials and sLORETA in parachuters","authors":"Haoran Zhang ,&nbsp;Zhenghao Fu ,&nbsp;Chenglong Cao ,&nbsp;Shuochen Wang ,&nbsp;Huanhuan Li ,&nbsp;Hang Xie ,&nbsp;Yang Zhou ,&nbsp;Xiang Li ,&nbsp;Jian Song","doi":"10.1016/j.neuroscience.2025.05.033","DOIUrl":"10.1016/j.neuroscience.2025.05.033","url":null,"abstract":"<div><div>Repetitive subconcussion, often overlooked due to subtle symptoms, but it can lead to cumulative neural alteration. Repetitive subconcussion, commonly arising from indirect brain trauma during sports or military activities, may affect emotional processing and cognition, yet their long-term effects are unclear. This study uses event-related potentials (ERP) and standardized low-resolution brain electromagnetic tomography (sLORETA) to assess the impact of repetitive subconcussive exposure on emotional processing in parachuters. Seventy-five parachuters, divided into low, medium, and high exposure groups based on training duration, and 25 healthy controls were recruited. Participants completed the Mini-Mental State Examination (MMSE) and Beck Depression Inventory-II (BDI-II) and viewed emotional images during EEG recording to measure late positive potential (LPP) amplitudes. sLORETA identified activation patterns in emotional processing regions. Correlation between the number of jumps and LPP amplitude and scale scores were analysed.Results: Compared to healthy controls, medium and high exposure groups exhibited reduced LPP amplitudes, indicating impaired emotional processing. sLORETA analysis revealed no differences in the low exposure group, reduced activation in BA6 for the medium group, and diminished activation in BA2, BA40, and BA46 for the high group. Jump frequency correlated negatively with LPP amplitudes and positively with BDI-II scores. The results demonstrate emotional processing impairment from repetitive subconcussion, with corresponding reductions in BA6, BA2, BA40, and BA46 activation. LPP amplitudes and activation in specific brain regions may serve as biomarkers for brain health assessment in exposed populations. This study highlights the risks of repetitive subconcussion, offering a foundation for targeted interventions.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 1-9"},"PeriodicalIF":2.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased GABAA receptor open probability: Adaptive mechanisms to cope with anoxia in the painted turtle","authors":"Haushe Suganthan ,&nbsp;Han Le ,&nbsp;Ahmed Elbassiouny ,&nbsp;Anthony Rajkumar ,&nbsp;Vineeth A. Raveendran ,&nbsp;Jessica C. Pressey ,&nbsp;Melanie A. Woodin ,&nbsp;Belinda S.W. Chang ,&nbsp;Leslie T. Buck","doi":"10.1016/j.neuroscience.2025.05.032","DOIUrl":"10.1016/j.neuroscience.2025.05.032","url":null,"abstract":"<div><div>The western painted turtle is the most anoxia-tolerant tetrapod known, surviving ∼ 4 months at 3 °C without oxygen. In the mammalian brain, absence of oxygen leads to hyper-excitability and cell death within minutes. A major mechanism by which painted turtles survive anoxia is a large increase of γ-aminobutyric acid (GABA) in the brain leading to a dominating Cl^- conductance that clamps membrane potential near the reversal potential of the GABA_A receptor. Whole-cell GABA_A receptor currents are known to increase with the onset of anoxia because of increased presynaptic GABA release, we hypothesized that GABA_A receptor currents may also exhibit a large increase due to increased channel open time. To investigate this, we used cell-attached single-channel patch-clamp electrophysiological techniques to measure GABA_A receptor open times (P_open) during a normoxic to anoxic transition in pyramidal neurons in turtle brain cortical sheets. GABA_A receptor P_open significantly increased 13-fold with the onset of anoxia and was blocked by the inclusion of the protein kinase C (PKC) activator PMA phorbol-12-myristate-13-acetate. Indicating the receptor was regulated by covalent modification. To investigate the molecular evolutionary mechanisms underlying these adaptations, we used codon-based likelihood models to detect changes in selective pressure amongst the GABA_A receptor subunit genes. We found positive selection in <em>GABRB2</em> and <em>GABRB3</em> at sites near their ligand binding interface, likely impacting channel kinetics associated with hypoxia-tolerance. The elucidation of the adaptations associated with increased hypoxia tolerance furthers our understanding of physiological adaptations to extreme low-oxygen environments.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"579 ","pages":"Pages 10-23"},"PeriodicalIF":2.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}