Brain Research Bulletin最新文献

{"title":"Arecoline alleviates autism spectrum disorder-like behaviors and cognition disorders in a valproic acid mouse model by activating the AMPK/CREB/BDNF signaling pathway","authors":"Chunyan Wen ,&nbsp;Zhizhong Xu ,&nbsp;Fengling Cao,&nbsp;Qianfa Yuan,&nbsp;Weichao Su,&nbsp;Zhiyuan Huang","doi":"10.1016/j.brainresbull.2025.111431","DOIUrl":"10.1016/j.brainresbull.2025.111431","url":null,"abstract":"<div><div>Studies in humans have revealed that the pathogenesis of autism spectrum disorder (ASD) is linked to white matter abnormalities involving hypomyelination and oligodendroglia dysfunction; however, effective treatments remain limited. Similarly, the valproic acid (VPA) model mice, which are widely used to study ASD, also exhibit white matter abnormalities with hypomyelination. Arecoline has been reported to enhance memory and cognition, facilitate myelination and improve neurological function. This study investigated the therapeutic potential of arecoline in a mouse model of prenatal VPA-induced ASD. We established an ASD mouse model through prenatal exposure to VPA and treated the mice with arecoline for 4 weeks. Behavioral analyses, including the elevated-plus maze, open field, self-grooming, marble-burying, three-chamber, Y-maze, and Morris water maze tests, were conducted to assess the effects of arecoline on behavior. Western blotting was used to detect changes in protein expression in the frontal cortex after arecoline treatment. The results revealed that offspring prenatally exposed to VPA presented characteristic behavioral abnormalities, including increased repetitive and stereotyped behaviors, deficits in social interaction, and impairments in learning and memory, accompanied by reduced expression of the myelin marker MBP and the mature oligodendrocyte marker GST-pi in the frontal cortex. Four-week arecoline treatment (1 and 2 mg/kg/day) significantly ameliorated these behavioral and cognitive abnormalities and restored myelination markers. Further mechanistic investigations demonstrated that arecoline enhanced the phosphorylation levels of AMPKα and CREB in the frontal cortex. This activation upregulated the expression of downstream BDNF, an essential neurotrophic factor for oligodendrocyte maturation and remyelination. These findings suggest that the AMPK/CREB/BDNF pathway may contribute to the therapeutic effects of arecoline, potentially through increased oligodendrocyte maturation and remyelination. This study provides preclinical evidence supporting arecoline as a potential myelination-targeting intervention, with implications for ASD and other neurological disorders involving myelination deficits.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111431"},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293308","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":"Associations among neuropsychological performance, brain structural alterations, and glymphatic function in patients with minimal hepatic encephalopathy","authors":"Chao Ju ,&nbsp;Longtao Yang ,&nbsp;Zhongshang Dai ,&nbsp;Yisong Wang ,&nbsp;Chang Li ,&nbsp;Wei Zhao ,&nbsp;Yongfang Jiang ,&nbsp;Haiyang Li ,&nbsp;Jun Liu","doi":"10.1016/j.brainresbull.2025.111416","DOIUrl":"10.1016/j.brainresbull.2025.111416","url":null,"abstract":"<div><div>Brain anatomical alterations in gray matter(GM), white matter(WM), and glymphatic system(GS) in patients with hepatitis B cirrhosis(HBC) with minimal hepatic encephalopathy(MHE) remain to be clarified. A total of 33 healthy controls and 37 patients with treatment-native primary HBC (further subdivided into HBC in MHE group[MHE] and HBC in non-MHE group[NMHE]) participated in neuroimaging study with three-dimensional T1 and a half q-space Cartesian grid diffusion model. Group differences in regional GM volume(GMV) were assessed using voxel-based morphometry(VBM) analysis. Differences in WM diffusion metrics were compared using tract-based spatial statistics(TBSS) analysis. Diffusion tensor image analysis along the perivascular space(DTI-ALPS) was employed to evaluate GS function. Compared to healthy control group (HC), GMV was reduced in MHE group, mainly in the vermis, bilateral pallidum, and right putamen, but was increased in right lateral geniculate thalamus(Thal_LGN_R) and left pulvinar medial thalamus(Thal_PuM_L). MHE patients displayed greater isotropic volume fraction(ISOVF) in the right sagittal stratum, right superior longitudinal fasciculus, left fornix(cres)/stria terminalis, left corticospinal tract, left cerebral peduncle, and left cingulum (hippocampus) than HC. DTI-ALPS was significantly downregulated in MHE patients. It revealed cortical changes, low-grade WM edema, and GS disorders at the early stage of chronic HBC, which will aid in MHE identification.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111416"},"PeriodicalIF":3.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222622","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":"Macrostructural and microstructural alterations of hippocampal subregions in T2DM: NODDI provides added value to DTI and volumetric analyses","authors":"Xuan Huang ,&nbsp;Ziyu Diao ,&nbsp;Die Shen ,&nbsp;Jianyu Li ,&nbsp;Jiahe Wang ,&nbsp;Kun Wang ,&nbsp;Shijun Qiu","doi":"10.1016/j.brainresbull.2025.111417","DOIUrl":"10.1016/j.brainresbull.2025.111417","url":null,"abstract":"<div><h3>Objective</h3><div>We explored macrostructural and microstructural changes in the hippocampal subregions of patients with type 2 diabetes mellitus (T2DM) and compared the effectiveness of neurite orientation dispersion and density imaging (NODDI) with that of traditional diffusion tensor imaging (DTI) and volumetric analysis in detecting structural alterations.</div></div><div><h3>Methods</h3><div>A total of 302 participants (128 T2DM patients and 174 healthy controls) underwent 3.0-T magnetic resonance imaging and neuropsychological assessments. Hippocampal subregions were segmented and registered using FreeSurfer and SPM, with DTI and NODDI analyses being performed to assess microstructural changes. Neuropsychological and clinical data were further analyzed to explore correlations with cognitive function.</div></div><div><h3>Results</h3><div>Significant microstructural alterations were observed in the hippocampal subregions of T2DM patients, with NODDI detecting abnormalities in approximately 70 % of the subregions, which were characterized by increased neurite density index (NDI), orientation dispersion index (ODI), and free water fraction (FWF) values, thus suggesting increased neurite density, disrupted orientation, and elevated free water content across most hippocampal subfields. DTI and NODDI analyses consistently identified the hippocampus-amygdala transition area (HATA) as a subregion that is particularly sensitive to microstructural changes in T2DM patients. Moreover, the NDI and FWF values were significantly correlated with cognitive performance, with the molecular layer and hippocampal tail exhibiting the strongest associations between microstructural indices and cognitive function.</div></div><div><h3>Conclusion</h3><div>This study reveals microstructural alterations in the hippocampal subregions of T2DM patients, with particular changes being observed in the HATA region, moreover, this study highlights the advantages of the NODDI model in detecting these subtle changes, thereby providing important theoretical insights for future research.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111417"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222445","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":"Oxytocin can ameliorate social deficits and brain developmental impairments in a rat model of early life excessive screen time exposure","authors":"Mozhan Parsa ,&nbsp;Monireh Mansouri ,&nbsp;Hamidreza Pouretemad","doi":"10.1016/j.brainresbull.2025.111419","DOIUrl":"10.1016/j.brainresbull.2025.111419","url":null,"abstract":"<div><div>In recent years studies have shown that early life excessive screen time exposure may significantly contribute to the emergence of social deficits and autistic-like behaviors. However, the exact underlying mechanisms and the optimal treatment strategies are not completely understood, with conflicting results of preceding findings. This study investigates the effect of oxytocin on autism-related behaviors, and associated brain structure abnormalities induced by excessive audiovisual stimulation (EAVS) as an early life excessive screen exposure model in rats. Neonatal rat pups were exposed to EAVS from postnatal day (PND) 12 to PND 35, and intranasal oxytocin (OXT) at a dose of 0.8 IU/kg was administrated from PND21 to PND35. Behavioral assessment including social interaction, repetitive behavior, locomotor activity, and anxiety-like behavior, along with three-dimensional brain structure measurements were done during adolescence (PND50-PND55). The results revealed EAVS-induced anomalies in social interaction, hyperactivity, and changes in the volume, and neuron number of brain regions including the amygdala and anterior cingulate cortex (ACC) in the EAVS group which were modulated by oxytocin. Our findings suggest that OXT may mitigate adverse effects of early life excessive exposure to digital screens, enhancing social preferences through modulating brain plasticity. The observed neuroanatomical and behavioral alterations highlight the vulnerability of the developing brain to early life excessive screen exposure and suggest a potential therapeutic path through OXT to tackle social impairments induced by EAVS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111419"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231894","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":"The role of prefrontal cortex in chronic low back pain with comorbid depression: A resting-state fMRI study","authors":"Yanqiao Zhao ,&nbsp;Chen Gong ,&nbsp;Pan Zhu ,&nbsp;Suimin Guo ,&nbsp;Yangyang Lin ,&nbsp;Yafei Wang ,&nbsp;Beibei Feng ,&nbsp;Xiaochun Meng ,&nbsp;Yuling Wang","doi":"10.1016/j.brainresbull.2025.111408","DOIUrl":"10.1016/j.brainresbull.2025.111408","url":null,"abstract":"<div><div>Patients with chronic low back pain (CLBP) experience comorbid depression. However, the central neural processing profile of CLBP with comorbid depression remains unclear. Therefore, this study aimed to investigate specific brain abnormalities in CLBP with comorbid depression by functional magnetic resonance imaging. Fourteen CLBP patients with depression, 25 CLBP patients without depression, and 24 matched controls were included. Alterations in spontaneous brain activity and connectivity were examined through regional homogeneity (ReHo) and functional connectivity (FC). Analysis of variance and post hoc analyses among groups were conducted. Correlational analyses were performed between neuroplasticity and clinical variables. Mediation analysis was conducted to elucidate the interrelationships among brain alterations, pain, and depression. Significant between-group differences in ReHo values were found across extensive brain regions, particularly the right dorsolateral prefrontal cortex (DLPFC). Altered FC between the DLPFC and cerebellum as well as the orbitofrontal cortex was noted. ReHo and FC were associated with depression, pain catastrophizing, and back pain-related disability. ReHo values of superior frontal gyrus and its FC to cerebellum mediated the correlation between BDI and variables such as pain intensity and pain catastrophizing. CLBP patients with comorbid depression exhibit abnormal regional homogeneity in regions involving the DLPFC, and altered functional networks are observed between the DLPFC and other areas. Central changes are correlated with back pain-related outcomes and mediate the relationship between pain and depression. Our findings contribute additional insights for identifying potential biomarkers of refractory CLBP with depression comorbidity, potentially aiding in pain phenotype stratification and optimizing pain management strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111408"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233261","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":"The role of microglia in neuropathic pain: A systematic review of animal experiments","authors":"Junyi Long ,&nbsp;Guihua Tian ,&nbsp;Ke He ,&nbsp;Youxiang Su ,&nbsp;Ziyao Wang ,&nbsp;Liangqing Huang ,&nbsp;Youmei Yao ,&nbsp;Xinyi Li ,&nbsp;Yi Lin","doi":"10.1016/j.brainresbull.2025.111410","DOIUrl":"10.1016/j.brainresbull.2025.111410","url":null,"abstract":"<div><h3>Background</h3><div>Neuropathic pain develops from lesions or diseases that affect the peripheral or central somatosensory nervous system. External factors causing nervous system damage may induce neuropathic pain, which is often refractory and profoundly impairs patients’ quality of life and functional capacity.</div></div><div><h3>Objective</h3><div>This study aims to evaluate animal studies on neuropathic pain in the past three years to elucidate the mechanism of microglia in neuropathic pain and to provide a theoretical basis for clinical treatment.</div></div><div><h3>Methods</h3><div>Literature searches were conducted through seven databases, including Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (VIPC), and SinoMed. The neuropathic pain model animals' pain indicators (thermal pain threshold, mechanical pain threshold), microglia-related findings, and related mechanism discoveries were extracted from the included studies.</div></div><div><h3>Results</h3><div>A total of 24 animal studies were included in this study. All studies showed that microglia exhibited an activated state in animal neuropathic pain models established by different methods. Twenty studies demonstrated that microglial activation exacerbates neuropathic pain by driving neuroinflammatory cascades. However, four studies confirmed that microglia could alleviate pain through the M2 phenotype and the release of endogenous opioid peptides.</div></div><div><h3>Conclusion</h3><div>The mediating effect of microglia on neuropathic pain is bidirectional. Pain-activated microglia do not necessarily exacerbate pain. Polarization toward the M2 phenotype or stimulation of endogenous opioid peptide release from microglia may attenuate pain. Overall, there are still many uncertainties about the mechanism of microglia in neuropathic pain. It is suggested to further study the neurobiological mechanism of this process to provide ideas for the design of future clinical trials.</div></div><div><h3>Registration</h3><div>PROSPERO (ID: CRD42024599437)</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111410"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222624","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":"Gray matter and white matter functional connectivity changes induced by rTMS concurrent with cognitive training in Alzheimer’s disease","authors":"Jicheng Fang ,&nbsp;Yan Shi ,&nbsp;Li Ba ,&nbsp;Min Zhang ,&nbsp;Muwei Li ,&nbsp;Ning Zheng ,&nbsp;Yuanyuan Qin ,&nbsp;Wenzhen Zhu","doi":"10.1016/j.brainresbull.2025.111418","DOIUrl":"10.1016/j.brainresbull.2025.111418","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Primarily by targeting the gray matter (GM), repetitive transcranial magnetic stimulation (rTMS) has shown promise in improving cognitive function in individuals with Alzheimer’s disease (AD). However, the impact of rTMS on white matter (WM) remains poorly understood. This study aimed to investigate the functional connectivity (FC) changes in both GM and WM induced by rTMS, and explore their relationship with the clinical manifestation of the disease.</div></div><div><h3>Methods</h3><div>Sixteen patients with mild to moderate AD were enrolled and randomly assigned to either the real rTMS group (n = 8) or the sham treatment group (n = 8). Both groups received cognitive training in combination with rTMS. The real rTMS group received 10 Hz stimulation targeting the left dorsolateral prefrontal cortex (DLPFC) followed by the left lateral temporal lobe (LTL), with each session lasting 20 min per day for 4 weeks, while sham with the coil positioned at a 90° angle. Resting-state BOLD signals were averaged to generate mean time series for each of the 82 GM regions and 48 WM bundles, both before and after treatment for each subject. We analyzed the resting-state fMRI data by using a 2 × 2 factorial design with “time” as the within-subjects factor and “group” as the between-subjects factor.</div></div><div><h3>Results</h3><div>In the analysis of 82 GM regions, when using left LTL as the seed, significant time main effect was observed in right ventral Posterior cingulate cortex (vPCC) (F=9.356, p = 0.009, η²=0.401) and right inferior temporal gyrus (ITG) (F=11.784, p = 0.004, η²=0.457). In the analysis of 48 WM bundles, when using left DLPFC as the seed, significant time × group interactions were found in right cingulum (hippocampus part, CGH) (F=12.123, p = 0.004, η²=0.464). The FC between left DLPFC and right cerebral peduncle (CBRP) demonstrated significant time main effect (F=15.569, p = 0.001, η²=0.527). Moreover, the FC between left DLPFC and right CGH was significantly correlated with MMSE scores changes (r = -0.610, p = 0.027), reflecting cognitive improvements after treatment.</div></div><div><h3>Conclusion</h3><div>The current study suggested that rTMS, when combined with cognitive training, can concurrently modulate functional activities in both GM and WM in patients with mild to moderate AD, which are associated with cognitive improvements. Notably, the limbic system appears to play a pivotal role in facilitating this therapeutic process.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111418"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212255","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":"TBX21 knockdown attenuates neuroinflammation induced by intracerebral hemorrhage via the SIRT1-WDR5-H3K4me3 axis","authors":"Zhichao Zou ,&nbsp;Zhi Liu ,&nbsp;Zhanwei Zhang ,&nbsp;Xiaojing Li","doi":"10.1016/j.brainresbull.2025.111415","DOIUrl":"10.1016/j.brainresbull.2025.111415","url":null,"abstract":"<div><div>Neuroinflammation is a key contributor to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). This study aimed to elucidate the role and underlying mechanisms of T-box transcription factor 21 (TBX21), a known regulator of type I inflammatory responses, in ICH-induced neuroinflammation. An <em>in vitro</em> oxygen-glucose deprivation (OGD) model using BV2 microglia and an <em>in vivo</em> autologous blood injection-induced ICH rat model were used to modulate TBX21 and sirtuin 1 (SIRT1) expression. The results showed that TBX21 knockdown significantly suppressed the OGD-induced release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), decreased levels of the oxidative stress marker malondialdehyde (MDA), and restored the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, TBX21 knockdown reversed the OGD-induced upregulation of TBX21, WDR5, H3K4me3, cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS), while enhancing SIRT1 expression. Mechanistically, TBX21 could directly bind to the promoter region of SIRT1 and suppress its transcription, and the protective effects of TBX21 knockdown were abolished by SIRT1 knockdown. In the ICH rat model, TBX21 knockdown or SIRT1 overexpression led to improvements in neurological severity scores, reductions in hematoma volume, and restoration of tight junction protein expression (occludin, claudin-3, and ZO-1). Collectively, these findings indicate that TBX21 promotes post-ICH neuroinflammation by repressing SIRT1, thereby enhancing WDR5-mediated H3K4me3 epigenetic modifications. TBX21 may therefore serve as a promising therapeutic target for mitigating SBI after ICH.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111415"},"PeriodicalIF":3.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224388","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":"Sodium-glucose cotransporter-2 inhibitor, dapagliflozin, reverses depressive-like behavior in a mouse model of post-traumatic stress disorder","authors":"Haneen Amawi ,&nbsp;Tayma Makhlouf ,&nbsp;Alaa M. Hammad ,&nbsp;Sahar Alsheyab ,&nbsp;Rawan Alhazaimeh ,&nbsp;F. Scott Hall ,&nbsp;Joyeeta T. Khan ,&nbsp;Bahaa Al-Trad ,&nbsp;Amit K. Tiwari","doi":"10.1016/j.brainresbull.2025.111414","DOIUrl":"10.1016/j.brainresbull.2025.111414","url":null,"abstract":"<div><h3>Background</h3><div>Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent psychological distress resulting from the experience of intense traumatic events, such as warfare or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are widely prescribed treatments for PTSD, but their adverse side effects are a significant concern and they have only limited efficacy as a symptomatic treatment for PTSD. Moreover, they have no effect on the core underlying causes of PTSD Studies have reported a potential neuroprotective effect for Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized the single-prolonged stress (SPS) mouse model of PTSD, which involved sequential exposure to different stressors (2 hours of restraint, 20 minutes of forced swimming, 15 minutes of rest, and 1–2 minutes of diethyl ether exposure), to investigate the therapeutic potential of Dapagliflozin (DAPA), a novel SGLTi, in mitigating the SPS-induced depressive-like behavior.</div></div><div><h3>Methods</h3><div>Male mice were randomly assigned to four experimental groups: Control group, SPS group, DAPA group (dapagliflozin; 1 mg/kg/day by oral gavage for 7 days), and SPS+DAPA group. Behavioral assessments for depressive-like behaviors were evaluated using the forced swim test and the tail suspension test. Blood and brain tissue samples were collected for analysis stress markers.</div></div><div><h3>Results</h3><div>SPS-treated mice showed significant depressive-like behavior on the seventh day post-treatment, which was reversed by DAPA treatment (1 mg/kg/day). Significant increases in brain tissue mRNA expression of <em>Crh, Bax, Il1b, and Bdnf</em>, as well as serum corticosterone, were observed in the SPS group, while DAPA reversed these effects.</div></div><div><h3>Conclusion</h3><div>This data indicates that DAPA (1 mg/kg) has potential therapeutic effects for the treatment of PTSD-induced depressive-like symptoms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111414"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204632","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":"The activity of glutamatergic neurons in the dorsal-ventral poles of the dentate gyrus regulates distinct phenotypes of depression in mice","authors":"Jinping Wang ,&nbsp;Hongjie Li ,&nbsp;Yusi Hua ,&nbsp;Lanyu Zhang ,&nbsp;Xiaoqin Jiang ,&nbsp;Xinchuan Wei","doi":"10.1016/j.brainresbull.2025.111413","DOIUrl":"10.1016/j.brainresbull.2025.111413","url":null,"abstract":"<div><div>Depression is a heterogeneous mental disorder. The dorsal and/or ventral dentate gyrus (DG) has been implicated in the pathophysiology of depression. However, it remains unclear whether the activities of glutamatergic neurons in the dorsal and ventral DG contribute to the heterogeneity of depression. In the present study, we conduct a series of depression-related behavior tests by activating or inhibiting the activity of glutamatergic neurons in the dorsal and ventral DG using chemical genetic methods. It is found that inhibiting the dorsal DG glutamatergic neurons induces social deficits, as well as learning and memory dysfunction, while activating them improves social behaviors and alleviated social deficits induced by chronic stress. Conversely, inhibiting the ventral DG glutamatergic neurons increases anxiety and despair-like symptoms, and activating them reduces anxiety and despair-like symptoms and alleviates these symptoms caused by chronic stress. Our study highlights the necessity of incorporating dorsoventral axis-specific analyses of DG in subsequent investigations to better understand the pathophysiological heterogeneity of depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111413"},"PeriodicalIF":3.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144196472","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}