Brain Research Bulletin最新文献

{"title":"Effects of aminooxyacetic acid on learning and memory function and neurochemical changes in chronic alcoholism","authors":"Hongbo Jiang ,&nbsp;Xunling Wang ,&nbsp;Yingwei Liang ,&nbsp;Yinghan Hou ,&nbsp;Xinping Yue ,&nbsp;Zhiyi Zhang ,&nbsp;Dan Chen ,&nbsp;Xinyi Fan ,&nbsp;Ailin Du","doi":"10.1016/j.brainresbull.2025.111203","DOIUrl":"10.1016/j.brainresbull.2025.111203","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effect of aminooxyacetic acid (AOAA) on cognitive function, particularly learning and memory, in a rat model of chronic alcoholism. Additionally, the study explored changes in cystathionine β-synthase (CBS), hydrogen sulfide (H₂S), and serotonin (5-HT) levels in the prefrontal cortex to understand the potential neurochemical mechanisms involved.</div></div><div><h3>Methods</h3><div>Sixty-four male SD rats were randomly divided into four groups, with 16 rats in each: Con, Con + AOAA, Model, and Model + AOAA. The Model group received a 6 % ethanol solution for 28 days. From day 14, the Model + AOAA group was treated with daily intraperitoneal injections of AOAA (5 mg/kg) for 14 consecutive days. Cognitive function was assessed using the Morris water maze, mitochondrial function was evaluated through ATPase activity, and H₂S levels were measured. CBS and 5-HT levels in the prefrontal cortex were analyzed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Compared to the control groups, rats in the Model group exhibited significant impairments in learning and memory, increased CBS expression, elevated H₂S levels, and decreased 5-HT release. AOAA treatment improved memory performance, reduced CBS expression and H₂S levels, and increased 5-HT release, although these measures did not fully return to baseline. No significant differences were observed between the two control groups.</div></div><div><h3>Conclusion</h3><div>AOAA may alleviate cognitive deficits associated with chronic alcoholism by inhibiting CBS expression, reducing H₂S levels, and enhancing 5-HT release in the prefrontal cortex. These findings suggest AOAA as a potential therapeutic strategy for alcohol-induced cognitive impairments.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111203"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in ischemic stroke: A meta-analysis of preclinical studies","authors":"Xiaoming Zhang ,&nbsp;Yibing Guo ,&nbsp;Kun Fang ,&nbsp;Xiangqian Huang ,&nbsp;Duo Lan ,&nbsp;Mengqi Wang ,&nbsp;Lina Jia ,&nbsp;Xunming Ji ,&nbsp;Ran Meng ,&nbsp;Da Zhou","doi":"10.1016/j.brainresbull.2025.111219","DOIUrl":"10.1016/j.brainresbull.2025.111219","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) remains a significant global health burden, necessitating the development of novel therapeutic strategies. This study aims to systematically evaluate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) on IS outcomes in rodent models.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across multiple databases to identify studies investigating the effects of MSC-Exos on rodent models of IS. Following rigorous inclusion and exclusion criteria, 73 high-quality studies were selected for meta-analysis. Primary outcomes included reductions in infarct volume/ratio and improvements in functional recovery scores. Data extraction and analysis were performed using RevMan 5.3 software.</div></div><div><h3>Results</h3><div>Pooled data indicated that MSC-Exos administration significantly reduced infarct size and improved functional recovery scores in rodent models of IS. Treatment within 24 hours and beyond 24 hours of stroke induction both demonstrated substantial reductions in infarct volume/ratio compared to controls. Furthermore, MSC-Exos-treated groups exhibited marked improvements in functional recovery, as assessed by various neurobehavioral tests. The meta-analysis showed no significant publication bias, and heterogeneity levels were acceptable.</div></div><div><h3>Conclusions</h3><div>MSC-Exos reveal significant therapeutic potential for IS, with evidence supporting their efficacy in reducing infarct size and enhancing functional recovery in preclinical rodent models. These findings pave the way for further research and potential clinical translation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111219"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in the vestibulothalamic pathway: Association with balance ability and subjective visual vertical of vestibular function","authors":"Sang Seok Yeo ,&nbsp;Seo Yoon Park ,&nbsp;In Hee Cho","doi":"10.1016/j.brainresbull.2025.111209","DOIUrl":"10.1016/j.brainresbull.2025.111209","url":null,"abstract":"<div><h3>Introduction</h3><div>The thalamus regulates various sensory information to each related brain area. The vestibular nucleus transmits information of motor control to the thalamus regulating coordination function. The vestibulothalamic tract (VTT) is a neural pathway between the vestibular nucleus and thalamus that processes vestibular information for postural balance and spatial perception. Therefore, this study analyzed ipsilateral VTT to compare the neural pathway and the differences in vestibular and balance functions according to aging.</div></div><div><h3>Methods</h3><div>Eleven elderly and 12 young healthy adults were recruited. This study measured subjective visual vertical (SVV) for vestibular function and body sway during one-leg standing. The ipsilateral VTT were reconstructed to investigate changes of neural pathway between two groups using diffusion tensor imaging.</div></div><div><h3>Results</h3><div>Track volume of left and right VTTs was significantly more in the young healthy adults. In eyes-open (EO) condition during one-leg standing, the body sway demonstrated significant differences between two groups. In the eyes-closed (EC) condition, the degree of hip sway was decreased in the young healthy adults. In the EO condition, the body sway except for antero-posterior direction was significantly correlated with VTT. Meanwhile, in the EC condition, hip sway and all values of body sway were negatively correlated with VTT. In addition, the VTT revealed a negative correlation with SVV.</div></div><div><h3>Conclusions</h3><div>The tract volume of VTT and static balance decreased according to aging. The changes of VTT also affected verticality perception and static balance. Therefore, the study could be helpful in providing the data for patients with thalamus or vestibular injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111209"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging features for cognitive fatigue and its recovery with VR intervention: An EEG microstates analysis","authors":"Jia-Cheng Han ,&nbsp;Chi Zhang ,&nbsp;Yan-Dong Cai ,&nbsp;Yu-Ting Li ,&nbsp;Yu-Xuan Shang ,&nbsp;Zhu-Hong Chen ,&nbsp;Guan Yang ,&nbsp;Jia-Jie Song ,&nbsp;Dan Su ,&nbsp;Ke Bai ,&nbsp;Jing-Ting Sun ,&nbsp;Yu Liu ,&nbsp;Na Liu ,&nbsp;Ya Duan ,&nbsp;Wen Wang","doi":"10.1016/j.brainresbull.2025.111223","DOIUrl":"10.1016/j.brainresbull.2025.111223","url":null,"abstract":"<div><h3>Introduction</h3><div>Cognitive fatigue is mainly caused by enduring mental stress or monotonous work, impairing cognitive and physical performance. Natural scene exposure is a promising intervention for relieving cognitive fatigue, but the efficacy of virtual reality (VR) simulated natural scene exposure is unclear. We aimed to investigate the effect of VR natural scene on cognitive fatigue and further explored its underlying neurophysiological alterations with electroencephalogram (EEG) microstates analysis.</div></div><div><h3>Methods</h3><div>Ten participants performed a 20-minute 1-back task before and after VR intervention while EEG was recorded (pre-task, post-task). Performance was measured with mean accuracy rate (MAR) and mean reaction time (MRT) of the continuous 1-back task. VR simulation of the Canal Town scene was utilized to alleviate cognitive fatigue caused by 1-back tasks. Four resting-state phases were identified: beginning, pre, post, and end phases.</div></div><div><h3>Results</h3><div>Post-task had a higher MAR and a lower MRT than pre-task. For pre-task, MAR was negatively correlated with trials, while MRT was positively correlated with trials. Four EEG microstates classes (A-D) were identified, and their temporal parameters (mean duration, time coverage and occurrence) and transition probabilities were calculated. After intervention, mean duration and time coverage of class B decreased, all parameters of class C increased, while all parameters of class D decreased. Transition probabilities between classes B and D decreased but increased between classes A and C.</div></div><div><h3>Conclusion</h3><div>VR simulation of Canal Town scene is a potentially effective method to alleviate cognitive fatigue. Microstate is an electrophysiological trait characteristic of cognitive fatigue and might be used to indicate the effect of VR intervention.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111223"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellum abnormalities in vascular mild cognitive impairment with depression symptom patients: A multimodal magnetic resonance imaging study","authors":"Yirong Chen ,&nbsp;Liling Chen ,&nbsp;Liyu Hu ,&nbsp;Jianjun Wang ,&nbsp;Jinhuan Zhang ,&nbsp;Hanqing Lyu ,&nbsp;Jinping Xu ,&nbsp;Jianxiang Chen ,&nbsp;Haibo Yu","doi":"10.1016/j.brainresbull.2025.111213","DOIUrl":"10.1016/j.brainresbull.2025.111213","url":null,"abstract":"<div><h3>Background</h3><div>Subcortical vascular mild cognitive impairment (svMCI) frequently occurs alongside depression symptoms, significantly affecting patients' quality of life. While cognitive decline and depression symptoms are linked to cerebellar changes, the specific relationship between these changes and cognitive status in svMCI patients with depression symptoms remains unclear.</div></div><div><h3>Objective</h3><div>This study aimed to investigates the gray matter volume and functional alterations in the cerebellum of svMCI patients, with and without depression symptoms, and their correlation with cognitive and depressive symptoms.</div></div><div><h3>Methods</h3><div>We enrolled 16 svMCI patients with depression symptoms (svMCI+D), 15 without (svMCI-D), and 12 normal controls (NC). Multimodal MRI scans were conducted, assessing gray matter volume and resting-state functional connectivity (RSFC) in the cerebellum. Correlations between RSFC and clinical scores from the Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD) were analyzed.</div></div><div><h3>Results</h3><div>Structural analysis indicated gray matter atrophy in left cerebellar lobules I_IV and VI (Cere6.L) in svMCI patients. svMCI+D patients showed reduced RSFC between Cere6.L and left cerebellar region IX and the left superior frontal gyrus (SFGdor.L). Both svMCI+D and svMCI-D groups showed increased RSFC between Cere6.L and the right caudate nucleus. RSFC between Cere6.L and SFGdor.L correlated negatively with HAMD scores in svMCI+D and positively with MoCA scores in svMCI-D. RSFC between Cere6.L and the right caudate nucleus also correlated positively with MoCA in the svMCI-D.</div></div><div><h3>Conclusion</h3><div>Cerebellar abnormalities, including the gray matter atrophy and RSFC changes, are associated with svMCI, particularly when depression symptoms are present. These results suggest potential diagnostic and therapeutic implications for svMCI and emphasize the need for further research on the cerebellum's role in cognitive and emotional disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111213"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulation of glutamatergic nervous system in sleep-wake states and general anesthesia","authors":"Wei Luo ,&nbsp;Meiyi Duan ,&nbsp;Enpeng Liang ,&nbsp;Siwei Wang ,&nbsp;Jie Yuan","doi":"10.1016/j.brainresbull.2025.111220","DOIUrl":"10.1016/j.brainresbull.2025.111220","url":null,"abstract":"<div><div>The sleep-wake states and general anesthesia share many neurophysiological similarities, as both involve reversible changes in consciousness and modulation of brain activity. This paper reviews the role of glutamatergic neurons, the brain's primary excitatory neurons, in regulating sleep-wake states and general anesthesia. We discuss the involvement of glutamatergic neurons across various brain regions, including the brainstem, basal forebrain, thalamus, hypothalamus, and cortex, highlighting their contributions to physiological sleep-wake and anesthesia modulation. Recent advancements in techniques such as optogenetics, chemogenetics, and neural tracing have enhanced our understanding of these neurons' functions. Understanding these mechanisms can lead to improved therapeutic strategies for sleep disorders and more precise anesthetic practices, providing new avenues for clinical intervention.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111220"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological modulation of Sigma-1 receptor ameliorates pathological neuroinflammation in rats with diabetic neuropathic pain via the AKT/GSK-3β/NF-κB pathway","authors":"Yuyu An ,&nbsp;Shanshan Cao ,&nbsp;Leilei Shi ,&nbsp;Yuhan Zhang ,&nbsp;Xin Wang ,&nbsp;Shiyu Yuan ,&nbsp;Yongheng Shi ,&nbsp;Bin Wang ,&nbsp;Jiping Liu ,&nbsp;Chao-jun Han","doi":"10.1016/j.brainresbull.2025.111226","DOIUrl":"10.1016/j.brainresbull.2025.111226","url":null,"abstract":"<div><div>Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1 mg/kg), and metformin (Met, 20 mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10 μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111226"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture combined with trigonelline inhibits pyroptosis in cerebral ischemia-reperfusion by suppressing autophagy via the PI3K/AKT/mTOR signaling pathway","authors":"Zhengguo Qiu ,&nbsp;Jianbing Ma ,&nbsp;Xiaqing Zhang ,&nbsp;Mingna Jiao ,&nbsp;Liqiang Zhi","doi":"10.1016/j.brainresbull.2025.111200","DOIUrl":"10.1016/j.brainresbull.2025.111200","url":null,"abstract":"<div><h3>Background</h3><div>Electroacupuncture <strong>(</strong>EA) and trigonelline (TG) have been reported to be beneficial in alleviating cerebral ischemia/reperfusion injury (CIRI). However, the synergistic effects of EA and TG in CIRI and the underlying mechanism have not been demonstrated.</div></div><div><h3>Methods</h3><div>Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and reperfusion (MCAO/R) to establish a CIRI model. Neurological deficit score was evaluated using Garcia’s scale. Cerebral infarction in rats was determined using TTC staining. Brain tissue morphology was assessed by HE staining. The expression of various proteins was measured using IF assay and western blot.</div></div><div><h3>Results</h3><div>EA or TG treatment could effectively ameliorate neurological disorders, attenuate cerebral infarction and reduce neuronal damage in brain tissue in CIRI rats. In addition, EA or TG treatment suppressed autophagy and pyroptosis in CIRI rats. More importantly, synergistic effects of EA and TG intervention in CIRI rats were observed in ameliorating neuronal damage and suppressing autophagy and pyroptosis, while Rapa, an inducer of autophagy, strengthened these effects in MCAO/R-induced rats. Furthermore. Rapa reversed EA in combination with TG-mediated improvement of neuronal damage and suppression of autophagy and pyroptosis in CIRI rats. Notably, the PI3K/AKT/mTOR pathway was inactivated in CIRI rats and EA combined with TG enhanced the activation of the PI3K/AKT/mTOR pathway. LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, stimulated autophagy and pyroptosis in CIRI rats and reversed EA combined with TG-mediated suppression of autophagy and pyroptosis.</div></div><div><h3>Conclusion</h3><div>EA combined with TG suppressed pyroptosis, which was dependent on inhibition of autophagy in CIRI rats through activation of the PI3K/AKT/mTOR signaling pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111200"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A-modified lncRNA GAS5 promotes M1-polarization of microglia in alcohol use disorder","authors":"Shuang Zhu ,&nbsp;Peng Wang ,&nbsp;Jian Hu","doi":"10.1016/j.brainresbull.2025.111215","DOIUrl":"10.1016/j.brainresbull.2025.111215","url":null,"abstract":"<div><div>Long noncoding RNA (lncRNA) are essential for modulating the onset and progression of alcohol use disorder (AUD). In this study, we investigated the molecular pathways through which lncRNA may contribute to AUD development. We assessed the expression levels of long noncoding RNA GAS5 (lncRNA GAS5) and microRNA-136–5p (miR-136–5p) in AUD tissue samples and cell lines using reverse transcription-quantitative polymerase chain reaction. Detection of GAS5 N6-methyladenosine (m6A) modifications, facilitated by alkylation repair homolog 5 (ALKBH5), was performed using RNA immunoprecipitation and RNA pull-down assays. The effect of GAS5 on the functionality of SH-SY5Y cells was evaluated using CCK-8 and Transwell assays. Our findings showed high levels of GAS5 expression in both AUD tissues and cell lines. Overexpression of GAS5 decreased the migratory capability of SH-SY5Y cells, whereas silencing GAS5 increased this ability. Bioinformatics analyses predicted a relationship between expression levels of miR-136–5p and GAS5, which was subsequently confirmed using dual-luciferase reporter assays. Additionally, we discovered that GAS5 acts as a sponge for miR-136–5p, leading to the upregulation of ATF2. Elevated levels of ATF2 are associated with M1 microglial polarization. In summary, m6A-modified GAS5 may influence the M1 polarization of microglia via the miR-136–5p/ATF2 pathway. Statistical evaluations were performed using GraphPad Prism V8.0, employing the student's t-test for comparisons between two groups, assuming a normal distribution and equal variances. When variances were unequal, but normality was maintained, the corrected Student's t-test was applied. The non-parametric Wilcoxon rank-sum test was used to analyze non-normally distributed data, and one-way ANOVA was used to compare three or more groups. Independent replication was ensured in the studies, with each experiment repeated at least three times and statistical significance was set at P &lt; 0.05.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111215"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway","authors":"Liang Cao ,&nbsp;Wei-Hong Yan ,&nbsp;Wenjun Pi ,&nbsp;Yi Zhang ,&nbsp;Yan-Xiang Xiong ,&nbsp;V. Wee Yong ,&nbsp;Mengzhou Xue ,&nbsp;Qing Li ,&nbsp;Chunfu Zheng ,&nbsp;Leiluo Yang","doi":"10.1016/j.brainresbull.2025.111217","DOIUrl":"10.1016/j.brainresbull.2025.111217","url":null,"abstract":"<div><div>Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both <em>in vitro</em> and <em>in vivo</em>, and they may play a critical role in recovery after spinal cord injury (SCI). GABA_B receptors (GABABRs) are expressed in Pkd2l1⁺ CSF-cNs. However, their role in Pkd2l1⁺ CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABA_BR expression in a murine model 7 d after SCI. We further discovered that GABA_BR activation enhanced the proliferation of Pkd2l1⁺ CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABA_BR primed quiescent Pkd2l1⁺ CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABA_BR activation enhances the NSC potential of Pkd2l1⁺ CSF-cNs, ultimately enabling post-SCI recovery in murine models.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111217"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}