Molecular BrainPub Date : 2025-02-10DOI: 10.1186/s13041-025-01180-3
Xue Wang, Xiangqi Shao, Liang Yu, Jianru Sun, Xiang-Sha Yin, Zhen Chen, Yuanyuan Xu, Naili Wang, Di Zhang, Wenying Qiu, Fan Liu, Chao Ma
{"title":"Changes in the pH value of the human brain in Alzheimer's disease pathology correlated with CD68-positive microglia: a community-based autopsy study in Beijing, China.","authors":"Xue Wang, Xiangqi Shao, Liang Yu, Jianru Sun, Xiang-Sha Yin, Zhen Chen, Yuanyuan Xu, Naili Wang, Di Zhang, Wenying Qiu, Fan Liu, Chao Ma","doi":"10.1186/s13041-025-01180-3","DOIUrl":"10.1186/s13041-025-01180-3","url":null,"abstract":"<p><p>The microenvironment of the central nervous system is highly complex and plays a crucial role in maintaining the function of neurons, which influences Alzheimer's disease (AD) progression. The pH value of the brain is a critical aspect of the brain microenvironment in regulating various physiological processes. However, the specific mechanisms and role of this mechanism are not yet fully understood. To better understand the relationship between brain pH and AD, we analyzed the brain pH of the frontal lobe and AD pathology scores in postmortem brain samples from 368 donors from the National Human Brain Bank for Development and Function, 96 of whom were diagnosed with AD pathology. Analysis revealed a significant decrease in brain pH in AD patients, which was strongly correlated with β-amyloid plaques and phosphorylated tau proteins. Here, we elucidated the differential protein expression level of CD68-positive microglia between control and AD groups (t = 3.198, df = 20, P = 0.0045), and its protein expression level was correlated negatively with the brain pH value (F = 26.93, p = 0.0006). Our findings revealed that increased activation of CD68-positive microglia and disrupted lysosomal homeostasis in the pathological brain tissue of individuals with AD may lead to a decrease in brain pH.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391382","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}
Molecular BrainPub Date : 2025-02-07DOI: 10.1186/s13041-025-01176-z
François Brial, Aurélie Le Lay, Claude Rouch, Edouard Henrion, Mathieu Bourgey, Guillaume Bourque, Mark Lathrop, Christophe Magnan, Dominique Gauguier
{"title":"Transcriptome atlases of rat brain regions and their adaptation to diabetes resolution following gastrectomy in the Goto-Kakizaki rat.","authors":"François Brial, Aurélie Le Lay, Claude Rouch, Edouard Henrion, Mathieu Bourgey, Guillaume Bourque, Mark Lathrop, Christophe Magnan, Dominique Gauguier","doi":"10.1186/s13041-025-01176-z","DOIUrl":"10.1186/s13041-025-01176-z","url":null,"abstract":"<p><p>Brain regions drive multiple physiological functions through specific gene expression patterns that adapt to environmental influences, drug treatments and disease conditions. To generate a detailed atlas of the brain transcriptome in the context of diabetes, we carried out RNA sequencing in hypothalamus, hippocampus, brainstem and striatum of the Goto-Kakizaki (GK) rat model of spontaneous type 2 diabetes, which was applied to identify gene transcription adaptation to improved glycemic control following vertical sleeve gastrectomy (VSG) in the GK. Over 19,000 distinct transcripts were detected in the rat brain, including 2794 which were consistently expressed in the four brain regions. Region-specific gene expression was identified in hypothalamus (n = 477), hippocampus (n = 468), brainstem (n = 1173) and striatum (n = 791), resulting in differential regulation of biological processes between regions. Differentially expressed genes between VSG and sham operated rats were only found in the hypothalamus and were predominantly involved in the regulation of endothelium and extracellular matrix. These results provide a detailed atlas of regional gene expression in the diabetic rat brain and suggest that the long term effects of gastrectomy-promoted diabetes remission involve functional changes in the hypothalamus endothelium.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"9"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370394","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":"Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway.","authors":"Huiqi Yuan, Yanan Xu, Hailun Jiang, Meizhu Jiang, Luofei Zhang, Shifeng Wei, Cao Li, Zhigang Zhao","doi":"10.1186/s13041-025-01178-x","DOIUrl":"10.1186/s13041-025-01178-x","url":null,"abstract":"<p><p>Recent studies have shown that abnormal activity of acid sphingomyelinase (Asm) has been associated with a range of psychiatric disorders including schizophrenia and depression. However, the role of Asm in the regulation of anxiety remains unclear. In the present study, we employed Asm-knockout (Asm KO) mice to investigate the association between Asm and anxiety using behavioral tests, RNA sequencing, q-PCR, immunohistochemical staining, and other methods. The behavioral results showed that Asm KO mice exhibit enhanced anxiety-like behaviors, such as restricted activity, reduced cumulative times in the central area, diminished exploratory interest, delayed latency to feed, through behavioral tests including open field, novelty-suppressed feeding test, elevated plus maze test, ect. Transcriptional profiling combined with bioinformatics analysis revealed the upregulation of Toll-like receptor signaling pathway related gene including Tlr1/2, Ccl3, Ccl4, Ccl5 and Cd86 in Asm KO mice, which was further confirmed by the detection of activated microglia and astrocytes through iba-1 and GFAP immunohistochemical staining. Collectively, our findings uncover a role for Asm in regulating anxiety-like behavior and suggest that it may be essential for the maintenance of emotional stability, indicating its potential as a promising target for treating anxiety disorders.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189462","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}
Molecular BrainPub Date : 2025-01-24DOI: 10.1186/s13041-025-01177-y
Kai Chen, Xingyu Du, Melissa A Chao, Zhongcong Xie, Guang Yang
{"title":"Surgery impairs glymphatic activity and cognitive function in aged mice.","authors":"Kai Chen, Xingyu Du, Melissa A Chao, Zhongcong Xie, Guang Yang","doi":"10.1186/s13041-025-01177-y","DOIUrl":"10.1186/s13041-025-01177-y","url":null,"abstract":"<p><p>Delirium is a common complication in elderly surgical patients and is associated with an increased risk of dementia. Although advanced age is a major risk factor, the mechanisms underlying postoperative delirium remain poorly understood. The glymphatic system, a brain-wide network of perivascular pathways, facilitates cerebrospinal fluid (CSF) flow and supports the clearance of metabolic waste. Impairments in glymphatic function have been observed in aging brains and various neurodegenerative conditions. Using in vivo two-photon imaging, we examined the effects of surgery (laparotomy) on glymphatic function in adult (6 months) and aged (18 months) mice 24 h post-surgery. In adult mice, CSF tracer entry into the brain parenchyma along periarteriolar spaces occurred rapidly following intracisternal tracer injection, with no significant differences between sham and surgery groups. In contrast, aged mice exhibited delayed tracer influx, with further impairments observed in the surgery group compared to sham controls. This glymphatic dysfunction correlated with poorer T-maze performance in aged mice. These findings suggest that surgery exacerbates glymphatic impairment in aging brains, potentially hindering brain waste clearance and contributing to postoperative delirium.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"7"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040318","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}
Molecular BrainPub Date : 2025-01-23DOI: 10.1186/s13041-025-01175-0
Ahmed Z Ibrahim, Kareem Abdou, Masanori Nomoto, Kaori Yamada-Nomoto, Reiko Okubo-Suzuki, Kaoru Inokuchi
{"title":"Sleep-driven prefrontal cortex coordinates temporal action and multimodal integration.","authors":"Ahmed Z Ibrahim, Kareem Abdou, Masanori Nomoto, Kaori Yamada-Nomoto, Reiko Okubo-Suzuki, Kaoru Inokuchi","doi":"10.1186/s13041-025-01175-0","DOIUrl":"10.1186/s13041-025-01175-0","url":null,"abstract":"<p><p>Cognitive processes such as action planning and decision-making require the integration of multiple sensory modalities in response to temporal cues, yet the underlying mechanism is not fully understood. Sleep has a crucial role for memory consolidation and promoting cognitive flexibility. Our aim is to identify the role of sleep in integrating different modalities to enhance cognitive flexibility and temporal task execution while identifying the specific brain regions that mediate this process. We have designed \"Auditory-Gated Patience-to-Action\" Task in which mice should process different auditory signals before action execution as well as analyzing the visual inputs for feedback of their action. Mice could learn the task rule and apply it only after sleeping period and could keep the performance constant across sessions. c-fos positive cells showed the involvement of prelimbic cortex (PrL) during task execution. Chemo-genetic inhibition verified that PrL is required for proper signal response and action timing. These findings emphasize that sleep and cortical activity are keys for cognitive flexibility in adapting to different modalities.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029118","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}
Molecular BrainPub Date : 2025-01-23DOI: 10.1186/s13041-025-01171-4
Tarek Shaker, Gwyneth J Dagpa, Vanessa Cattaud, Brian A Marriott, Mariam Sultan, Mohammed Almokdad, Jesse Jackson
{"title":"Correction: A simple and reliable method for claustrum localization across age in mice.","authors":"Tarek Shaker, Gwyneth J Dagpa, Vanessa Cattaud, Brian A Marriott, Mariam Sultan, Mohammed Almokdad, Jesse Jackson","doi":"10.1186/s13041-025-01171-4","DOIUrl":"10.1186/s13041-025-01171-4","url":null,"abstract":"","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"5"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029115","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}
Molecular BrainPub Date : 2025-01-23DOI: 10.1186/s13041-025-01173-2
Yang Zhang, Miaowen Jiang, Di Wu, Ming Li, Xunming Ji
{"title":"The causal relationship between steroid hormones and risk of stroke: evidence from a two-sample Mendelian randomization study.","authors":"Yang Zhang, Miaowen Jiang, Di Wu, Ming Li, Xunming Ji","doi":"10.1186/s13041-025-01173-2","DOIUrl":"10.1186/s13041-025-01173-2","url":null,"abstract":"<p><p>It is unclear how steroid hormones contribute to stroke, and conducting randomized controlled trials to obtain related evidence is challenging. Therefore, Mendelian randomization (MR) technique was employed in this study to examine this association. Through genome-wide association meta-analysis, the genetic variants of steroid hormones, including testosterone/17β-estradiol (T/E2) ratio, aldosterone, androstenedione, progesterone, and hydroxyprogesterone, were acquired as instrumental variables. Analysis was done on the impact of these steroid hormones on the risk of stroke subtypes. The T/E2 ratio was associated to an elevated risk of small vessel stroke (SVS) according to the inverse variance weighted approach which was the main MR analytic technique (OR, 1.23, 95% CI: 1.05-1.44, p = 0.009). These findings were solid since no heterogeneity nor horizontal pleiotropy were found. The causal association between T/E2 and SVS was also confirmed in the replication study (p = 0.009). Nevertheless, there was no proof that other steroid hormones increased the risk of stroke. According to this study, T/E2 ratio and SVS are causally related. However, strong evidence for the impact of other steroid hormones on stroke subtypes is still lacking. These findings may be beneficial for developing stroke prevention strategies from steroid hormones levels.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"6"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029121","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}
Molecular BrainPub Date : 2025-01-21DOI: 10.1186/s13041-025-01172-3
Dan Li, Shuijing Cao, Yanrong Chen, Yueyan Liu, Kugeng Huo, Zhuangqi Shi, Shuxin Han, Liecheng Wang
{"title":"Distribution and functional significance of KLF15 in mouse cerebellum.","authors":"Dan Li, Shuijing Cao, Yanrong Chen, Yueyan Liu, Kugeng Huo, Zhuangqi Shi, Shuxin Han, Liecheng Wang","doi":"10.1186/s13041-025-01172-3","DOIUrl":"10.1186/s13041-025-01172-3","url":null,"abstract":"<p><p>Kruppel-like factor 15 (KLF15), a member of the KLF family, is closely involved in many biological processes. However, the mechanism by which KLF15 regulates neural development is still unclear. Considering the complexity and importance of neural network development, in this study, we investigated the potent regulatory role of KLF15 in neural network development. KLF15 was detected highly expressed in the cerebellum and enriched in Purkinje cells, with a significant increase in KLF15 expression between 15 and 20 days of neural development. Knockdown of KLF15 led to loss of Purkinje cells and impaired motility in mice. Therefore, our study aims to elucidate the relationship between KLF15 and Purkinje cells in mice, may provide a new research idea for the developmental mechanism of the mouse cerebellum.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008514","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}
Molecular BrainPub Date : 2025-01-14DOI: 10.1186/s13041-025-01174-1
Randall J Eck, Paul N Valdmanis, Nicole F Liachko, Brian C Kraemer
{"title":"Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.","authors":"Randall J Eck, Paul N Valdmanis, Nicole F Liachko, Brian C Kraemer","doi":"10.1186/s13041-025-01174-1","DOIUrl":"10.1186/s13041-025-01174-1","url":null,"abstract":"<p><p>Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice. Some conservation exists between alternative polyadenylation in rNLS8 mice and human disease models including in disease relevant genes and biological pathways. Together, these findings support both TDP-43 loss and toxic gain-of-function phenotypes as contributors to the neurodegeneration in rNLS8 mice, nominating its continued utility as a preclinical model for investigating mechanisms of neurodegeneration in ALS/FTLD-TDP.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984290","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}