Frontiers in Cellular Neuroscience最新文献

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LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1495546
Jiandong Sun, Weiju Lin, Xiaoning Hao, Michel Baudry, Xiaoning Bi
{"title":"LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition.","authors":"Jiandong Sun, Weiju Lin, Xiaoning Hao, Michel Baudry, Xiaoning Bi","doi":"10.3389/fncel.2024.1495546","DOIUrl":"10.3389/fncel.2024.1495546","url":null,"abstract":"<p><p>Intracellular lysosomal trafficking and positioning are fundamental cellular processes critical for proper neuronal function. Among the diverse array of proteins involved in regulating lysosomal positioning, the Transient Receptor Potential Mucolipin 1 (TRPML1) and the Ragulator complex have emerged as central players. TRPML1, a lysosomal cation channel, has been implicated in lysosomal biogenesis, endosomal/lysosomal trafficking including in neuronal dendrites, and autophagy. LAMTOR1, a subunit of the Ragulator complex, also participates in the regulation of lysosomal trafficking. Here we report that LAMTOR1 regulates lysosomal positioning in dendrites of hippocampal neurons by interacting with TRPML1. LAMTOR1 knockdown (KD) increased lysosomal accumulation in proximal dendrites of cultured hippocampal neurons, an effect reversed by TRPML1 KD or inhibition. On the other hand, TRPML1 activation with ML-SA1 or prevention of TRPML1 interaction with LAMTOR1 using a TAT-decoy peptide induced dendritic lysosomal accumulation. LAMTOR1 KD-induced proximal dendritic lysosomal accumulation was blocked by the dynein inhibitor, ciliobrevin D, suggesting the involvement of a dynein-mediated transport. These results indicate that LAMTOR1-mediated inhibition of TRPML1 is critical for normal dendritic lysosomal distribution and that release of this inhibition or direct activation of TRPML1 results in abnormal dendritic lysosomal accumulation. The roles of LAMTOR1-TRPML1 interactions in lysosomal trafficking and positioning could have broad implications for understanding cognitive disorders associated with lysosomal pathology and calcium dysregulation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1495546"},"PeriodicalIF":4.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800094","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}
引用次数: 0
Neuroinflammation and major depressive disorder: astrocytes at the crossroads.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1504555
Melissa Puentes-Orozco, Sonia L Albarracin, María Marcela Velásquez
{"title":"Neuroinflammation and major depressive disorder: astrocytes at the crossroads.","authors":"Melissa Puentes-Orozco, Sonia L Albarracin, María Marcela Velásquez","doi":"10.3389/fncel.2024.1504555","DOIUrl":"10.3389/fncel.2024.1504555","url":null,"abstract":"<p><p>Major depressive disorder is a complex and multifactorial condition, increasingly linked to neuroinflammation and astrocytic dysfunction. Astrocytes, along with other glial cells, beyond their classic functions in maintaining brain homeostasis, play a crucial role in regulating neuroinflammation and neuroplasticity, key processes in the pathophysiology of depression. This mini-review explores the involvement of astrocytes in depression emphasizing their mediation in neuroinflammation processes, the impact of astrocytic dysfunction on neuroplasticity, and the effect of some antidepressants on astrocyte reactivity. Recent evidence suggests that targeting astrocyte-related signaling pathways, particularly the balance between different astrocytic phenotypes, could offer promising evidence for therapeutic strategies for affective disorders. Therefore, a deeper understanding of astrocyte biology may open the way to innovative treatments aimed at mitigating depressive symptoms by impacting both neuroinflammation and imbalances in neuroplasticity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1504555"},"PeriodicalIF":4.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800020","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}
引用次数: 0
A crosstalk between autophagy and apoptosis in intracerebral hemorrhage.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1445919
Moyan Wang, Xin Chen, Shuangyang Li, Lingxue Wang, Hongmei Tang, Yuting Pu, Dechou Zhang, Bangjiang Fang, Xue Bai
{"title":"A crosstalk between autophagy and apoptosis in intracerebral hemorrhage.","authors":"Moyan Wang, Xin Chen, Shuangyang Li, Lingxue Wang, Hongmei Tang, Yuting Pu, Dechou Zhang, Bangjiang Fang, Xue Bai","doi":"10.3389/fncel.2024.1445919","DOIUrl":"10.3389/fncel.2024.1445919","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a severe condition that devastatingly harms human health and poses a financial burden on families and society. Bcl-2 Associated X-protein (Bax) and B-cell lymphoma 2 (Bcl-2) are two classic apoptotic markers post-ICH. Beclin 1 offers a competitive architecture with that of Bax, both playing a vital role in autophagy. However, the interaction between Beclin 1 and Bcl-2/Bax has not been conjunctively analyzed. This review aims to examine the crosstalk between autophagy and apoptosis in ICH by focusing on the interaction and balance of Beclin 1, Bax, and Bcl-2. We also explored the therapeutic potential of Western conventional medicine and traditional Chinese medicine (TCM) in ICH via controlling the crosstalk between autophagy and apoptosis.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1445919"},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800088","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}
引用次数: 0
Bridging the gap of vision restoration.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1502473
Maya Carleton, Nicholas W Oesch
{"title":"Bridging the gap of vision restoration.","authors":"Maya Carleton, Nicholas W Oesch","doi":"10.3389/fncel.2024.1502473","DOIUrl":"10.3389/fncel.2024.1502473","url":null,"abstract":"<p><p>Retinitis pigmentosa (RP) and Age-Related Macular Degeneration (AMD) are similar in that both result in photoreceptor degeneration leading to permanent progressive vision loss. This affords the possibility of implementing vision restoration techniques, where light signaling is restored to spared retinal circuitry to recreate vision. There are far more AMD patients (Wong et al., 2014), yet more resources have been put towards researching and developing vision restoration strategies for RP despite it rarity, because of the tractability of RP disease models. The hope is that these therapies will extend to the AMD population, however, many questions remain about how the implementation of prosthetic or optogenetic vision restoration technologies will translate between RP and AMD patients. In this review, we discuss the difference and similarities of RP and AMD with a focus on aspects expected to impact vision restoration strategies, and we identify key gaps in knowledge needed to further improve vision restoration technologies for a broad patient population.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1502473"},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784409","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}
引用次数: 0
MAM-mediated mitophagy and endoplasmic reticulum stress: the hidden regulators of ischemic stroke.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1470144
Ziyi Jia, Hongtao Li, Ke Xu, Ruobing Li, Siyu Yang, Long Chen, Qianwen Zhang, Shulin Li, Xiaowei Sun
{"title":"MAM-mediated mitophagy and endoplasmic reticulum stress: the hidden regulators of ischemic stroke.","authors":"Ziyi Jia, Hongtao Li, Ke Xu, Ruobing Li, Siyu Yang, Long Chen, Qianwen Zhang, Shulin Li, Xiaowei Sun","doi":"10.3389/fncel.2024.1470144","DOIUrl":"10.3389/fncel.2024.1470144","url":null,"abstract":"<p><p>Ischemic stroke (IS) is the predominant subtype of stroke and a leading contributor to global mortality. The mitochondrial-associated endoplasmic reticulum membrane (MAM) is a specialized region that facilitates communication between the endoplasmic reticulum and mitochondria, and has been extensively investigated in the context of neurodegenerative diseases. Nevertheless, its precise involvement in IS remains elusive. This literature review elucidates the intricate involvement of MAM in mitophagy and endoplasmic reticulum stress during IS. PINK1, FUNDC1, Beclin1, and Mfn2 are highly concentrated in the MAM and play a crucial role in regulating mitochondrial autophagy. GRP78, IRE1, PERK, and Sig-1R participate in the unfolded protein response (UPR) within the MAM, regulating endoplasmic reticulum stress during IS. Hence, the diverse molecules on MAM operate independently and interact with each other, collectively contributing to the pathogenesis of IS as the covert orchestrator.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1470144"},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784490","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}
引用次数: 0
Regulation of CeA-Vme projection in masseter hyperactivity caused by restraint stress.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1509020
Ya-Juan Zhao, Ji Chen, Yang Liu, Lv-La Pan, Yan-Xia Guo, Zhou-Ming Zhang, Qiang Li, Yong-Jin Chen
{"title":"Regulation of CeA-Vme projection in masseter hyperactivity caused by restraint stress.","authors":"Ya-Juan Zhao, Ji Chen, Yang Liu, Lv-La Pan, Yan-Xia Guo, Zhou-Ming Zhang, Qiang Li, Yong-Jin Chen","doi":"10.3389/fncel.2024.1509020","DOIUrl":"10.3389/fncel.2024.1509020","url":null,"abstract":"<p><p>The overactivity of the masticatory muscles (bruxism or teeth clenching) is associated with stress exposure, and often leading to consistent muscle pain. However, the neural mechanism underlining it is not fully understood. The central amygdala (CeA), which is linked to stress-induced behaviors and physical reactions, projects directly to the mesencephalic trigeminal nucleus (Vme), which is crucial for oral-motor coordination. Thus, we hypothesized that the projections from the CeA to the Vme could be linked to stress-induced anxiety and overactivity of the jaw muscles. After establishing an animal model of restraint stress, we found that chronic stress could lead to noticeable anxiety-related behavior, increased masseter muscle activity, activation of GABAergic neurons in the CeA, and opposite changes in the excitability of multipolar GABAergic interneurons and pseudounipolar excitatory neurons in the Vme. Subsequently, through the utilization of anterograde and transsynaptic tracing in conjunction with immunofluorescence staining, we discovered that the neural projections from the CeA to the Vme were mainly GABAergic and that the projections from the CeA terminated on GABAergic interneurons within the Vme. Moreover, chemogenetically suppressing the function of GABAergic neurons in the CeA could effectively reduce anxiety levels and reverse the increase in the activity of the masseter muscles induced by stress. And, specifically inhibiting GABAergic projections from the CeA to the Vme via optogenetics could reduce the hyperactivity of the masseter muscles but not stress-induced anxiety. In conclusion, our findings indicate that GABAergic projections from the CeA to the Vme may play an important role in the masseter overactivity in response to chronic stress.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1509020"},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784518","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}
引用次数: 0
Loss of Cdc42 causes abnormal optic cup morphogenesis and microphthalmia in mouse.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-20 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1474010
Katrina S Hofstetter, Paula M Haas, Jonathon P Kuntz, Yi Zheng, Sabine Fuhrmann
{"title":"Loss of Cdc42 causes abnormal optic cup morphogenesis and microphthalmia in mouse.","authors":"Katrina S Hofstetter, Paula M Haas, Jonathon P Kuntz, Yi Zheng, Sabine Fuhrmann","doi":"10.3389/fncel.2024.1474010","DOIUrl":"10.3389/fncel.2024.1474010","url":null,"abstract":"<p><p>Congenital ocular malformations originate from defective morphogenesis during early eye development and cause 25% of childhood blindness. Formation of the eye is a multi-step, dynamic process; it involves evagination of the optic vesicle, followed by distal and ventral invagination, leading to the formation of a two-layered optic cup with a transient optic fissure. These tissue folding events require extensive changes in cell shape and tissue growth mediated by cytoskeleton mechanics and intercellular adhesion. We hypothesized that the Rho GTPase Cdc42 may be an essential, convergent effector downstream of key regulatory factors required for ocular morphogenesis. CDC42 controls actin remodeling, apicobasal polarity, and junction assembly. Here we identify a novel essential function for Cdc42 during eye morphogenesis in mouse; in <i>Cdc42</i> mutant eyes expansion of the ventral optic cup is arrested, resulting in microphthalmia and a wide coloboma. Our analyses show that Cdc42 is required for expression of the polarity effector proteins PRKCZ and PARD6, intercellular junction protein tight junction protein 1, <i>β</i>-catenin, actin cytoskeleton F-actin, and contractile protein phospho myosin light chain 2. Expression of RPE fate determinants OTX2 and MITF, and formation of the RPE layer are severely affected in the temporal domain of the proximal optic cup. EdU incorporation is significantly downregulated. In addition, mitotic retinal progenitor cells mislocalize deeper, basal regions, likely contributing to decreased proliferation. We propose that morphogenesis of the ventral optic cup requires Cdc42 function for coordinated optic cup expansion and establishment of subretinal space, tissue tension, and differentiation of the ventral RPE layer.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1474010"},"PeriodicalIF":4.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800099","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}
引用次数: 0
The clinical perspective of circular RNAs in neurodegenerative diseases: potential diagnostic tools and therapeutic targets.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-18 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1470641
Xin'ai Li, Peng Wang, Shuo Qi, Jingwei Zhou, Jeremiah Amalraj, Junhui Wang, Zhiguo Ding
{"title":"The clinical perspective of circular RNAs in neurodegenerative diseases: potential diagnostic tools and therapeutic targets.","authors":"Xin'ai Li, Peng Wang, Shuo Qi, Jingwei Zhou, Jeremiah Amalraj, Junhui Wang, Zhiguo Ding","doi":"10.3389/fncel.2024.1470641","DOIUrl":"https://doi.org/10.3389/fncel.2024.1470641","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) mostly occur in older demographics. With the average lifespan increasing over time, NDDs are becoming one of the major adverse factors affecting human health and the quality of life. Currently, there are no specific diagnostic methods for NDDs and they are usually diagnosed based on nonspecific clinical symptoms and occasionally by biomarkers, such as <i>β</i>-amyloid (Aβ) for Alzheimer's disease (AD) and a-synuclein (<i>α</i>-syn) for Parkinson's disease, etc. However, it is usually too late for most treatment to startr when the aforementioned criteria become detectable. Circular RNAs (circRNAs) are a type of single-stranded, covalently closed, non-coding RNAs that lack a 5' cap structure and 3' terminal poly-A tail. According to recent research, circRNAs may play a crucial role for the onset and progression of some NDDs. These small RNAs may be potential diagnostic and prognostic markers and therapeutic targets for these diseases. This review will provide a comprehensive overview of the recent advancements of knowledge on the functions and the possible underlying mechanism of circRNAs in the pathogenesis and treatment of NDDs.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1470641"},"PeriodicalIF":4.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767737","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}
引用次数: 0
Maintenance of a central high frequency synapse in the absence of synaptic activity.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-18 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1404206
Sascha Lessle, Lena Ebbers, Yvette Dörflinger, Simone Hoppe, Michaela Kaiser, Hans Gerd Nothwang, Christoph Körber
{"title":"Maintenance of a central high frequency synapse in the absence of synaptic activity.","authors":"Sascha Lessle, Lena Ebbers, Yvette Dörflinger, Simone Hoppe, Michaela Kaiser, Hans Gerd Nothwang, Christoph Körber","doi":"10.3389/fncel.2024.1404206","DOIUrl":"https://doi.org/10.3389/fncel.2024.1404206","url":null,"abstract":"<p><p>Activity has long been considered essential for circuit formation and maintenance. This view has recently been challenged by proper synaptogenesis and only mildly affected synapse maintenance in the absence of synaptic activity in forebrain neurons. Here, we investigated whether synaptic activity is necessary for the development and maintenance of the calyx of Held synapse. This giant synapse located in the auditory brainstem is highly specialized to maintain high frequency, high-fidelity synaptic transmission for prolonged times and thus shows particularly high synaptic activity. We expressed the protease tetanus toxin light chain (TeNT) exclusively in bushy cells of the ventral cochlear nucleus (VCN) of juvenile mice. Since globular bushy cells give rise to the calyx of Held, expression of TeNT in these cells specifically abolished synaptic transmission at the calyx without impairing general functionality of the central auditory system. Calyces lacked synaptic activity after two weeks of TeNT expression. However, this did not lead to major changes in presynaptic morphology, the number of active zones (AZs) or the composition of postsynaptic AMPA-type glutamate receptors (GluAs). Moreover, the fenestration of the calyx of Held, a hallmark of structural maturation, occurred normally. We thus show that the maintenance of a specialized high frequency synapse in the auditory brainstem occurs in a hardwired, probably genetically encoded, manner with little dependence on synaptic activity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1404206"},"PeriodicalIF":4.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767733","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}
引用次数: 0
Time-dependent phenotypical changes of microglia drive alterations in hippocampal synaptic transmission in acute slices.
IF 4.2 3区 医学
Frontiers in Cellular Neuroscience Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.3389/fncel.2024.1456974
Laura Ferrucci, Bernadette Basilico, Ingrid Reverte, Francesca Pagani, Giorgia Scaringi, Federica Cordella, Barbara Cortese, Gaia De Propris, Andrea Galeone, Letizia Mazzarella, Alessandro Mormino, Stefano Garofalo, Azka Khan, Valeria De Turris, Valentina Ferretti, Paola Bezzi, Cornelius Gross, Daniele Caprioli, Cristina Limatola, Silvia Di Angelantonio, Davide Ragozzino
{"title":"Time-dependent phenotypical changes of microglia drive alterations in hippocampal synaptic transmission in acute slices.","authors":"Laura Ferrucci, Bernadette Basilico, Ingrid Reverte, Francesca Pagani, Giorgia Scaringi, Federica Cordella, Barbara Cortese, Gaia De Propris, Andrea Galeone, Letizia Mazzarella, Alessandro Mormino, Stefano Garofalo, Azka Khan, Valeria De Turris, Valentina Ferretti, Paola Bezzi, Cornelius Gross, Daniele Caprioli, Cristina Limatola, Silvia Di Angelantonio, Davide Ragozzino","doi":"10.3389/fncel.2024.1456974","DOIUrl":"https://doi.org/10.3389/fncel.2024.1456974","url":null,"abstract":"<p><p>It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding the role of microglia in synaptic regulation is derived from studies in acute brain slices. However, it is still uncertain to what extent the preparation and maintenance of acute slices can influence microglial function and whether microglial changes may affect synaptic transmission. In this study, we examined the impact of acute slice resting time on hippocampal CA1 microglia, by assessing morphological and functional parameters at two distinct time intervals. We report that after 4 h from slicing microglia undergo morphological, functional, and transcriptional changes, including a decrease in the number of branches and in their movement speed. Furthermore, microglia acquire a reactive phenotype, characterized by increased amplitude of outward rectifying K<sup>+</sup> currents, increased expression of the pro-inflammatory cytokine Tnfα and altered expression of the microglial receptors Cx3cr1 and P2y12r. We also examined time-dependent changes of excitatory synaptic transmission in CA1 pyramidal neurons from acute hippocampal slices, reporting time-dependent decrease in both amplitude and frequency of postsynaptic currents (sEPSCs), along with a decrease in spine density. Noticeably, sEPSCs amplitude decrease was absent in slices prepared from PLX5622 microglia-depleted mice, suggesting that this time-dependent effect on synaptic transmission is microglia-dependent. Our findings highlight possible causal relation between microglia phenotypic changes in the hours following slice preparation and concomitant synaptic changes, pointing to the mechanisms of acute synaptic modulation, whose understanding is crucial for unraveling microglia-neurons interplay in nature. Furthermore, they emphasize the potential issues associated with experimental time windows in ex vivo samples.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1456974"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767742","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}
引用次数: 0
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