Molecular BrainPub Date : 2024-09-20DOI: 10.1186/s13041-024-01143-0
Kiki Chen, Kousha Changizi Ashtiani, Roudabeh Vakil Monfared, Pierre Baldi, Amal Alachkar
{"title":"Circadian cilia transcriptome in mouse brain across physiological and pathological states.","authors":"Kiki Chen, Kousha Changizi Ashtiani, Roudabeh Vakil Monfared, Pierre Baldi, Amal Alachkar","doi":"10.1186/s13041-024-01143-0","DOIUrl":"10.1186/s13041-024-01143-0","url":null,"abstract":"<p><p>Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes' peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts' oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia's spatiotemporal dynamics in brain functions.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291530","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 : 2024-09-12DOI: 10.1186/s13041-024-01140-3
Denise Riquelme, Nicole Juanchuto-Viertel, Carlos Álamos, Elias Leiva-Salcedo
{"title":"TRPM4 inhibition slows neuritogenesis progression of cortical neurons","authors":"Denise Riquelme, Nicole Juanchuto-Viertel, Carlos Álamos, Elias Leiva-Salcedo","doi":"10.1186/s13041-024-01140-3","DOIUrl":"https://doi.org/10.1186/s13041-024-01140-3","url":null,"abstract":"TRPM4 is a non-selective cation channel activated by intracellular Ca2+ but only permeable to monovalent cations, its activation regulates membrane potential and intracellular calcium. This channel participates in the migration and adhesion of non-excitable cells and forms an integral part of the focal adhesion complex. In neurons, TRPM4 expression starts before birth and its function at this stage is not clear, but it may function in processes such as neurite development. Here we investigate the role of TRPM4 in neuritogenesis. We found that neurons at DIV 0 express TRPM4, the inhibition of TRPM4 using 9-Ph reduces neurite number and slows the progression of neurite development, keeping neurons in stage 1. The genetic suppression of TRPM4 using an shRNA at later stages (DIV2) reduces neurite length. Conversely, at DIV 0, TRPM4 inhibition augments the Cch-induced Ca2 + i increase, altering the calcium homeostasis. Together, these results show that TRPM4 participates in progression of neurite development and suggest a critical role of the calcium modulation during this stage of neuronal development.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221068","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":"Simulated weightlessness procedure, head-down bed rest has reversible effects on the metabolism of rhesus macaque.","authors":"Yuting Li, Xu Zhang, Zhen Xu, Xixia Chu, Zhiqiang Hu, Zhengyang Ye, Caiqin Li, Zhenbo Wang, Bin Zeng, Jingyu Pan, Qian Zhao, Chengbin Zhou, Zhaohui Lan, Guanghan Kan, Guang He, Xiaodan Xu, Weidong Li","doi":"10.1186/s13041-024-01133-2","DOIUrl":"10.1186/s13041-024-01133-2","url":null,"abstract":"<p><p>It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126172","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 : 2024-09-02DOI: 10.1186/s13041-024-01132-3
Jiyoung Choi, Yumei Wu, Daehun Park
{"title":"Absence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes.","authors":"Jiyoung Choi, Yumei Wu, Daehun Park","doi":"10.1186/s13041-024-01132-3","DOIUrl":"10.1186/s13041-024-01132-3","url":null,"abstract":"<p><p>ATG9A is the only integral membrane protein among core autophagy-related (ATG) proteins. We previously found that ATG9A does not co-assemble into synaptophysin-positive vesicles, but rather, localizes to a distinct pool of vesicles within synapsin condensates in both fibroblasts and nerve terminals. The endocytic origin of these vesicles further suggests the existence of different intracellular sorting or segregation mechanisms for ATG9A and synaptophysin in cells. However, the precise underlying mechanism remains largely unknown. In this follow-up study, we investigated the endosomal localization of these two proteins by exploiting the advantages of a Rab5 mutant that induces the formation of enlarged endosomes. Notably, ATG9A and synaptophysin intermix perfectly and do not segregate on giant endosomes, indicating that the separation of these two proteins is not solely caused by the inherent properties of the proteins, but possibly by other unknown factors.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120238","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 reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia.","authors":"Yu-Sha Liao, Tie-Chun Zhang, Yu-Qi Tang, Pei Yu, Ya-Ning Liu, Jing Yuan, Ling Zhao","doi":"10.1186/s13041-024-01135-0","DOIUrl":"10.1186/s13041-024-01135-0","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120239","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 : 2024-09-02DOI: 10.1186/s13041-024-01137-y
Jeong-Woo Hwang, Jeongha Kim, Jin-Hee Park, Jinhan Nam, Ji-Yeong Jang, Aran Jo, Hyun-Ju Lee, Hyang-Sook Hoe
{"title":"Felodipine attenuates neuroinflammatory responses and tau hyperphosphorylation through JNK/P38 signaling in tau-overexpressing AD mice.","authors":"Jeong-Woo Hwang, Jeongha Kim, Jin-Hee Park, Jinhan Nam, Ji-Yeong Jang, Aran Jo, Hyun-Ju Lee, Hyang-Sook Hoe","doi":"10.1186/s13041-024-01137-y","DOIUrl":"10.1186/s13041-024-01137-y","url":null,"abstract":"<p><p>We previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120240","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 : 2024-09-02DOI: 10.1186/s13041-024-01138-x
Dylan J Terstege, Duneesha Goonetilleke, Cindy K Barha, Jonathan R Epp
{"title":"Running-induced neurogenesis reduces CA1 perineuronal net density without substantial temporal delay.","authors":"Dylan J Terstege, Duneesha Goonetilleke, Cindy K Barha, Jonathan R Epp","doi":"10.1186/s13041-024-01138-x","DOIUrl":"10.1186/s13041-024-01138-x","url":null,"abstract":"<p><p>Aerobic exercise has many effects on brain function, particularly at the hippocampus. Exercise has been shown to increase the rate of adult neurogenesis within the dentate gyrus and decrease the density of perineuronal nets in area CA1. The relationship between the rate of neurogenesis and the density of perineuronal nets in CA1 is robust; however, these studies only ever examined these effects across longer time scales, with running manipulations of 4 weeks or longer. With such long periods of manipulation, the precise temporal nature of the relationship between running-induced neurogenesis and reduced perineuronal net density in CA1 is unknown. Here, we provided male and female mice with home cage access to running wheels for 0, 1, 2, or 4 weeks and quantified hippocampal neurogenesis and CA1 perineuronal net density. In doing so, we observed a 2-week delay period prior to the increase in neurogenesis, which coincided with the same delay prior to decreased CA1 perineuronal net density. These results highlight the closely linked temporal relationship between running-induced neurogenesis and decreased perineuronal net expression in CA1.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120252","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":"Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-β measurements: a resting-state fMRI study.","authors":"Mohammad Sadeghi, Ali Azargoonjahromi, Hamide Nasiri, Arash Yaghoobi, Maryam Sadeghi, Seyedeh Saeideh Chavoshi, Shilan Baghaeikia, Nastaran Mahzari, Arina Valipour, Romina Razeghi Oskouei, Farshad Shahkarami, Fatemeh Amiri, Mahsa Mayeli","doi":"10.1186/s13041-024-01136-z","DOIUrl":"10.1186/s13041-024-01136-z","url":null,"abstract":"<p><p>Mild Cognitive Impairment (MCI) is a neurological condition characterized by a noticeable decline in cognitive abilities that falls between normal aging and dementia. Along with some biomarkers like GAP-43, Aβ, tau, and P-tau, brain activity and connectivity are ascribed to MCI; however, the link between brain connectivity changes and such biomarkers in MCI is still being investigated. This study explores the relationship between biomarkers like GAP-43, Aβ, tau, and P-tau, and brain connectivity. We enrolled 25 Participants with normal cognitive function and 23 patients with MCI. Levels of GAP-43, Aβ1-42, t-tau, and p-tau181p in the CSF were measured, and functional connectivity measures including ROI-to-voxel (RV) correlations and the DMN RV-ratio were extracted from the resting-state fMRI data. P-values below 0.05 were considered significant. The results showed that in CN individuals, higher connectivity within the both anterior default mode network (aDMN) and posterior DMN (pDMN) was associated with higher levels of the biomarker GAP-43. In contrast, MCI individuals showed significant negative correlations between DMN connectivity and levels of tau and P-tau. Notably, no significant correlations were found between Aβ levels and connectivity measures in either group. These findings suggest that elevated levels of GAP-43 indicate increased functional connectivity in aDMN and pDMN. Conversely, elevated levels of tau and p-tau can disrupt connectivity through various mechanisms. Thus, the accumulation of tau and p-tau can lead to impaired neuronal connectivity, contributing to cognitive decline.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109621","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":"Astrocyte-derived dominance winning reverses chronic stress-induced depressive behaviors.","authors":"Kyungchul Noh, Junyoung Oh, Woo-Hyun Cho, Minkyu Hwang, Sung Joong Lee","doi":"10.1186/s13041-024-01134-1","DOIUrl":"10.1186/s13041-024-01134-1","url":null,"abstract":"<p><p>Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080961","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 : 2024-08-22DOI: 10.1186/s13041-024-01130-5
Jane Jung, Jugeon Park, Sihyeon Park, Chul Hoon Kim, Hosung Jung
{"title":"Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway.","authors":"Jane Jung, Jugeon Park, Sihyeon Park, Chul Hoon Kim, Hosung Jung","doi":"10.1186/s13041-024-01130-5","DOIUrl":"10.1186/s13041-024-01130-5","url":null,"abstract":"<p><p>Protocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036424","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}