Xue Shi , Jingdong Zhang , Huangying Zhao , Hongjun Li , Junyi Zhu , Huangui Xiong
{"title":"Differential tissue and cellular distribution of chemokine C-C motif ligand 2 in grey/white matters of healthy and simian immunodeficiency virus infected monkey","authors":"Xue Shi , Jingdong Zhang , Huangying Zhao , Hongjun Li , Junyi Zhu , Huangui Xiong","doi":"10.1016/j.brainresbull.2025.111291","DOIUrl":"10.1016/j.brainresbull.2025.111291","url":null,"abstract":"<div><div>Previous studies have shown that CCL2 concentration is higher in cerebrospinal fluid than in plasma of health and human immunodeficiency virus (HIV) infected individuals, suggesting an extra source of CCL2 in brain. Brain cellular CCL2 has been broadly studied in cultured cells and its <em>in-vivo</em> cellular distribution has been investigated in rodent experimental autoimmune encephalomyelitis model. However, its cellular distribution in grey and white matter (GM, WM) remains elusive. We explored this issue using healthy and simian immunodeficiency virus (SIV) infected monkeys and found: <strong>1)</strong> Neurons were a major source of CCL2-like immunoreactivity (CCL2-ir) in normal GM, and corpus callosum (CC) ependyma showed high density of CCL2-ir. <strong>2)</strong> Upon SIV infection, CCL2-ir was strikingly raised in GM neurons, and in CC ependyma. <strong>3)</strong> Brain vascular-perivascular cells were a large source of CCL2-ir in normal GM and WM, which was relatively larger in CC WM than in GM. <strong>4)</strong> Vascular-perivascular CCL2-ir proportional areas were significantly enhanced by SIV infection in both GM and CC WM. <strong>5)</strong> Microglia seemed not to express CCL2 in healthy brain. Microglia-marker and CCL2-ir co-labeled cells were significantly increased by SIV infection. <strong>6)</strong> A vast of macrophage-like cells were situated along infected CC ependyma, suggesting a large number of monocytes be crossing ependyma, which may be related to establishment of viral reservoir. In conclusion, our study provides valuable insights into the cellular sources and alterations of CCL2 in the monkey brain under normal and SIV-infected conditions, which may promote better understanding of CCL2 in related neurological processes.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111291"},"PeriodicalIF":3.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584764","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}
Sophia E.G. Christoph , Karl T. Boden , Rudolf Siegel , Berthold Seitz , Peter Szurman , André Schulz
{"title":"The prevalence of Charles-Bonnet syndrome in ophthalmic patients: A systematic review and meta-analysis","authors":"Sophia E.G. Christoph , Karl T. Boden , Rudolf Siegel , Berthold Seitz , Peter Szurman , André Schulz","doi":"10.1016/j.brainresbull.2025.111282","DOIUrl":"10.1016/j.brainresbull.2025.111282","url":null,"abstract":"<div><h3>Objectives</h3><div>Charles Bonnet Syndrome (CBS) involves visually impaired yet mentally healthy individuals experiencing visual hallucinations (VH) while being aware of the hallucinations’ unreality. Its prevalence varies across different conditions<em>,</em> with low vision, bilateral vision loss and advanced age being established as risk factors. This meta-analysis aims to comprehensively assess CBS literature with regard to CBS prevalence in ophthalmic patients.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted on June 11th and June 13th 2023, using the databases PubMed/MEDLINE and Web of Science. Data evaluation and extraction was accomplished by two separate authors. Study analysis was performed qualitatively, thereafter quantitatively by a subsequent meta-analysis, including subgroup assessments for variations among demographic and ophthalmic variables.</div></div><div><h3>Results</h3><div>49 eligible studies were identified, encompassing data from 20 303 patients. The collective prevalence of CBS in literature was determined to be 10.2 % (95 % confidence interval: 7.23 % – 14.1 %). Vision rehabilitation patients suffer most frequently from CBS (24.6 %). Patients with retinal diseases, low vision, and glaucoma suffer from CBS at similar rates. The prevalence of CBS among these cohorts spans from 11.8 % to 17.7 %. Age (p = 0.0013) and sex (p = 0.003) correlated statistically significantly with the prevalence of CBS.</div></div><div><h3>Conclusions</h3><div>CBS is prevalent among ophthalmic patients with various eye diseases, especially in the presence of low vision. Ophthalmologists should consider that about one in six patients with retinal diseases, glaucoma, or low vision they assessed might experience CBS. Awareness among medical professionals should be increased, as education provides patients with relief.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111282"},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562596","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}
Brian Premchand , Kyaw Kyar Toe , Chuanchu Wang , Kai Rui Wan , Thevapriya Selvaratnam , Valerie Ethans Toh , Wai Hoe Ng , Camilo Libedinsky , Weiguo Chen , Ruiqi Lim , Ming-Yuan Cheng , Yuan Gao , Kai Keng Ang , Rosa Qi Yue So
{"title":"Comparing a BCI communication system in a patient with Multiple System Atrophy, with an animal model","authors":"Brian Premchand , Kyaw Kyar Toe , Chuanchu Wang , Kai Rui Wan , Thevapriya Selvaratnam , Valerie Ethans Toh , Wai Hoe Ng , Camilo Libedinsky , Weiguo Chen , Ruiqi Lim , Ming-Yuan Cheng , Yuan Gao , Kai Keng Ang , Rosa Qi Yue So","doi":"10.1016/j.brainresbull.2025.111289","DOIUrl":"10.1016/j.brainresbull.2025.111289","url":null,"abstract":"<div><div>Paralysis affects many people worldwide, and the people affected often suffer from impaired communication. We developed a microelectrode-based Brain-Computer Interface (BCI) for enabling communication in patients affected by paralysis, and implanted it in a patient with Multiple System Atrophy (MSA), a neurodegenerative disease that causes widespread neural symptoms including paralysis. To verify the effectiveness of the BCI system, it was also tested by implanting it in a non-human primate (NHP). Data from the human and NHP were used to train binary classifiers two different types of machine learning models: a Linear Discriminant Analysis (LDA) model, and a Long Short-Term Memory (LSTM)-based Artificial Neural Network (ANN). The LDA model performed at up to 72.7 % accuracy for binary decoding in the human patient, however, performance was highly variable and was much lower on most recording days. The BCI system was able to accurately decode movement vs non-movement in the NHP (accuracy using LDA: 82.7 ± 3.3 %, LSTM: 83.7 ± 2.2 %, 95 % confidence intervals), however it was not able to with recordings from the human patient (accuracy using LDA: 47.0 ± 5.1 %, LSTM: 44.6 ± 9.9 %, 95 % confidence intervals). We discuss how neurodegenerative diseases such as MSA can impede BCI-based communication, and postulate on the mechanisms by which this may occur.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111289"},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572190","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}
Jie Wang, Yanping Ma, Haiping Zhang, Na Li, Hangrui Xu, Yanan Liang, Meiling Luo, Yonghui Wang
{"title":"Swallowing cortical network features under taste stimulation for patients with post stroke dysphagia—Insights from a fNIRS study","authors":"Jie Wang, Yanping Ma, Haiping Zhang, Na Li, Hangrui Xu, Yanan Liang, Meiling Luo, Yonghui Wang","doi":"10.1016/j.brainresbull.2025.111287","DOIUrl":"10.1016/j.brainresbull.2025.111287","url":null,"abstract":"<div><div>The alterations in the swallowing cortical network associated with taste stimulation in patients with post-stroke dysphagia remain unclear. The aim of the study was to investigate the alterations in brain functional activity among individuals with post-stroke dysphagia under taste stimuli using functional near-infrared spectroscopy (fNIRS). We recruited 28 patients with post-stroke dysphagia and 24 age-matched healthy controls in this study. Each of them completed swallowing evaluation, resting-state and swallowing task-related fNIRS test. We found that the brain activation of patients significantly decreased in the left and right supplemental motor area (SMA) for water swallowing task and the left SMA and right primary sensory area (S1) for salty water swallowing, compared with healthy controls, only the left SMA remained significant for salty water swallowing after False Discovery Rate (FDR) correction. Fourteen healthy controls and 13 patients were included in the subgroup analysis, to explore the influences of preferred taste on swallowing network, we observed that the brain activation in the right S1 was significantly reduced during water swallowing in patient group (<em>p</em> = 0.008, with FDR corrected), all channels showed similar strengths in the activation under preferred taste stimulus between the groups. Functional connectivity (FC) between hemispheric sensorimotor areas were significantly decreased in patients compared with healthy controls. Our investigation revealed a noteworthy reduction in the activation of the left SMA during the salty water swallowing task in patients with dysphagia when compared to the healthy control group. The dysphagic patients following stroke exhibited impaired interaction between hemispheric sensorimotor areas associated with swallowing. Sour, sweet, and preferred taste stimulation have the potential to enhance brain plasticity, which may offer new insights for developing novel strategies for post-stroke dysphagia.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111287"},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572191","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}
Hailong Ge , Lujia Si , Chen Li , Junjie Huang , Limin Sun , Lan Wu , Yinping Xie , Ling Xiao , Gaohua Wang
{"title":"Tas2r123-associated mitochondrial organization and neuroplasticity underlying the antidepressant effect of resveratrol","authors":"Hailong Ge , Lujia Si , Chen Li , Junjie Huang , Limin Sun , Lan Wu , Yinping Xie , Ling Xiao , Gaohua Wang","doi":"10.1016/j.brainresbull.2025.111271","DOIUrl":"10.1016/j.brainresbull.2025.111271","url":null,"abstract":"<div><h3>Background</h3><div>Resveratrol, a natural bitter polyphenol, exhibits significant antidepressant property. Numerous studies have linked its antidepressant effect to neuroplasticity enhancement or mitochondrial regulation. However, the interplay between these two mechanisms remains unclear. This study aims to elucidate the relationship among resveratrol’s antidepressant effect, its regulatory impact on neuroplasticity and mitochondrial function, and to investigate the potential role of the type 2 bitter taste receptors (Tas2rs) in these processes.</div></div><div><h3>Methods</h3><div>A chronic unpredictable mild stress (CUMS) model was used to induce depressive-like behaviors, while resveratrol was administered as an intervention. Following CUMS and resveratrol treatment, proteomic analysis combined with bioinformatics predicted significantly altered biological pathways in the hippocampus. The aforementioned predictions were validated using Western blotting (WB), Golgi staining, Nissl staining, and electron microscopy. Additionally, Tas2rs expression and calcium (Ca<sup>2 +</sup>) levels in the hippocampus were quantified using quantitative PCR, WB, and calcium assay kit. Finally, immunofluorescence (IF) colocalization was used to examine the association of Tas2r123 with mitochondrial outer membrane in hippocampus.</div></div><div><h3>Results</h3><div>Resveratrol significantly alleviated depressive-like behaviors induced by CUMS. Proteomic analysis revealed that resveratrol’s therapeutic effects are associated with neuroplasticity-related and metabolic pathways, particularly with differentially expressed proteins (DEPs) predominantly localized in the mitochondria. Gene Ontology analysis of mitochondrial DEPs further revealed substantial changes in mitochondrial organization. Furthermore, molecular biology experiments validated these proteomics findings. Additionally, resveratrol also reversed the CUMS-induced downregulation of Tas2r123 mRNA and protein expression. Moreover, IF colocalization demonstrated a strong association between Tas2r123 and mitochondria.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that resveratrol may exert antidepressant property by modulating neuroplasticity through the Tas2r123-mitochondrial organization pathway. This study introduces a novel perspective linking Tas2rs to resveratrol’s antidepressant mechanisms, potentially pave the way for future antidepressant therapies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111271"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540322","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}
Manli Zhang , Hao Yu , Gongpeng Cao , Jinguo Huang , Yintao Cheng , Wenjing Zhang , Xiaotong Yuan , Rui Yang , Qiunan Li , Lixin Cai , Guixia Kang
{"title":"Three-branch feature enhancement and fusion network for focal cortical dysplasia lesions segmentation using multimodal imaging","authors":"Manli Zhang , Hao Yu , Gongpeng Cao , Jinguo Huang , Yintao Cheng , Wenjing Zhang , Xiaotong Yuan , Rui Yang , Qiunan Li , Lixin Cai , Guixia Kang","doi":"10.1016/j.brainresbull.2025.111268","DOIUrl":"10.1016/j.brainresbull.2025.111268","url":null,"abstract":"<div><h3>Objective</h3><div>Conventional multimodal imaging, including MRI and fluorodeoxyglucose positron emission tomography (FDG-PET), has difficulty in accurately detecting subtle or blurred focal cortical dysplasia (FCD) lesions. Morphometric maps assist localization by highlighting abnormal regions, whereas wavelet-filtered images emphasize texture and edge details. Therefore, we propose a three-branch feature enhancement and fusion network (TBFEF-Net) that integrates conventional multimodal imaging, morphometric maps, and wavelet-filtered images to enhance the accuracy of FCD localization.</div></div><div><h3>Methods</h3><div>The proposed TBFEF-Net comprises a semantic segmentation backbone, a cross-branch feature enhancement (CFE) module, and a multi-feature fusion (MFF) module. In the semantic segmentation backbone, three UNet-based branches separately extract semantic features from conventional multimodal imaging, morphometric maps, and wavelet-filtered images. In the encoding stage, the CFE incorporates a residual-based convolutional block attention module (CBAM) to aggregate features from all branches, enhancing the feature representation of FCD lesions. While in the decoding stage, the MFF integrates edge detail features from the wavelet-filtered imaging branch into the conventional multimodal imaging branch, enhancing the ability to capture lesion edges. As a result, this approach enables more precise segmentation.</div></div><div><h3>Results</h3><div>Experimental results show that TBFEF-Net surpasses several state-of-the-art methods in FCD segmentation. In the primary cohort, the Dice and sensitivity reached 59.73 % and 67.13 %, respectively, while in the open cohort, the Dice and sensitivity were 54.67 % and 54.81 %, respectively.</div></div><div><h3>Significance</h3><div>We introduced wavelet-filtered images for the first time in FCD segmentation, offering a novel approach and perspective for FCD lesions localization.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111268"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512139","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}
Jiapei Xie , Weidong Zhang , Yan Bai , Wei Wei , Yu Shen , Wanyue Li , Xinhui Wang , Chen Yu , Jiayin Pan , Xiaodong Jia , Hongjian Liu , Meiyun Wang
{"title":"Neural mechanisms of tinnitus: An exploration from the perspective of varying severity levels","authors":"Jiapei Xie , Weidong Zhang , Yan Bai , Wei Wei , Yu Shen , Wanyue Li , Xinhui Wang , Chen Yu , Jiayin Pan , Xiaodong Jia , Hongjian Liu , Meiyun Wang","doi":"10.1016/j.brainresbull.2025.111250","DOIUrl":"10.1016/j.brainresbull.2025.111250","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the brain functional changes in tinnitus patients of varying severities, in order to elucidate the complex relationship between tinnitus symptoms and neural mechanisms, providing a basis for personalized treatment for tinnitus patients with varying severity levels.</div></div><div><h3>Method</h3><div>62 patients with chronic tinnitus were divided into severe and mild tinnitus group. 31 healthy controls (HC) matched for age, gender and education level were included. Resting-state functional magnetic resonance imaging was performed for all subjects, and the values of regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and functional connectivity (FC) were calculated. One-way analysis of variance (ANOVA) was used to compare the differences among the three groups. Correlational analysis was conducted between imaging metrics and clinical information.</div></div><div><h3>Results</h3><div>Compared to the mild tinnitus, the severe tinnitus shows increased ReHo and ALFF values in the left superior temporal gyrus (STG), middle temporal gyrus (MTG), supramarginal gyrus (SMG), angular gyrus (ANG), and middle occipital gyrus (MOG), as well as increased ReHo values in the left superior frontal gyrus (SFG) and ALFF values in the right ANG. In the severe tinnitus group, the FC between the bilateral ANG and the left MTG, the right ANG and the right medial SFG, the right ANG and the right anterior cingulate gyrus (ACG), as well as between the left SFG and the left rectus gyrus, was increased compared to the mild tinnitus group. In mild tinnitus group, the ReHo of left STG is correlated with tinnitus severity by Tinnitus Handicap Inventory.</div></div><div><h3>Conclusion</h3><div>Patients with different severity of tinnitus exhibit different compensatory mechanisms in brain function, highlighting the need for stratified analysis based on severity when investigating the underlying neural mechanisms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111250"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405791","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}
Xing-Yu Lu , Jun-Fei Teng , Juan Yao , Xuan Li , Bing Wu , Xue-Qiang Hu , Ping Wang , Xiao-Qian Jiang , Jian-Feng Sui , Ke-Hui Hu , Yue-Ming Xu , Shu-Lei Liu
{"title":"The projection from the prelimbic cortex to the ventral tegmental area negatively regulates 5-HT-induced itch-scratching and positively regulates itch-related aversion in rats","authors":"Xing-Yu Lu , Jun-Fei Teng , Juan Yao , Xuan Li , Bing Wu , Xue-Qiang Hu , Ping Wang , Xiao-Qian Jiang , Jian-Feng Sui , Ke-Hui Hu , Yue-Ming Xu , Shu-Lei Liu","doi":"10.1016/j.brainresbull.2025.111283","DOIUrl":"10.1016/j.brainresbull.2025.111283","url":null,"abstract":"<div><div>Direct and indirect evidence suggests that the prelimbic cortex (PrL) and the ventral tegmental area (VTA) are the key brain regions involved in the regulation of itch sensation and itch-related emotions. The PrL projects widely to various cortical and subcortical brain regions, with the VTA being one of the main targets of PrL descending projections. However, the differential roles of the PrL-VTA pathway in the regulation of itch sensation and itch-related emotion remain unclear. In this study, we investigated 5-HT-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of PrL-VTA projection activity. Pharmacogenetic inhibition of a subpopulation of PrL glutamatergic neurons projecting to the VTA increased 5-HT-induced itch-scratching behavior but alleviated the conditioned place aversion behavior accompanying acute itch, indicating that the descending pathway from the PrL to the VTA negatively controls itch sensation but positively regulates itch-related negative emotion. GABAergic and DAergic neurons in the VTA are potentially responsible for mediating the opposite regulatory effects of PrL-VTA projections on itch sensation and emotion, respectively. These results are helpful for further understanding the neuroregulatory mechanisms of different components of itch.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111283"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527484","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}
Meimei Wu , Wenxin He , Huashan Gong , Li Dong , Na Ding , Guohua Zhang , Jing Wang , Weifang Rong
{"title":"The spatial and temporal pattern of GPER/GPR30 reporter expression in the developing and mature forebrain of mice","authors":"Meimei Wu , Wenxin He , Huashan Gong , Li Dong , Na Ding , Guohua Zhang , Jing Wang , Weifang Rong","doi":"10.1016/j.brainresbull.2025.111276","DOIUrl":"10.1016/j.brainresbull.2025.111276","url":null,"abstract":"<div><div>Evidence suggest that estrogens play crucial roles in the regulation of neural development and function and the G protein-coupled estrogen receptor (GPER/GPR30) appears to be the predominant estrogen receptor in the brain. However, the distribution and functions of GPER in the developing and mature brain are not fully understood. The current study aimed to characterize the expression of GPER in the forebrain, using <em>Gper</em> gene reporter mice combined with fluorescent in situ hybridization (FISH/RNAscope) and immunohistochemistry (IHC). Two lines of <em>Gper</em> reporter mice were constructed by crossing the <em>Gper</em>-cre mice with Ai14(RCL-tdT)-D or R26-ZsGreen mice, which showed identical spatial distributions of the reporters in adult brain. In the forebrain, neurons, protoplasmic astrocytes, mural cells and ependymal cells of third ventricle, were found to express <em>Gper</em> reporters. GPER-expressing neurons were particularly enriched in the olfactory system and the salience network, including posteromedial nucleus of the cortical amygdala (PmCo), entorhinal cortex, insula cortex, prefrontal cortex and dentate gyrus of the hippocampus. RNAscope and neural tracing showed GPER-expressing cortical neurons were long-range excitatory pyramidal neurons. GPER-expressing astrocytes represented a minor population (<10 %) of astrocytes and were found to be closely associated with neurovascular units. GPER-expressing mural cells were not labelled by the common pericyte marker PDGFRβ. In the critical period of neural development (P1-P10), GPER expression appeared to be intimately associated with neurogenesis, proliferation and migration in the olfactory system and the salience network. Collectively, the spatial and temporal pattern of GPER/GPR30 expression in the forebrain implied it might play important roles regulating the development and functions of the olfactory system, the salience network and the cerebral vessels.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111276"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534092","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}