Frontiers in Cellular Neuroscience最新文献

{"title":"Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.","authors":"Dong-Won Lee, Hae-Chul Park, Dong Hwee Kim","doi":"10.3389/fncel.2024.1441827","DOIUrl":"https://doi.org/10.3389/fncel.2024.1441827","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated <i>Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry)</i> zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389287","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":"Editorial: 15 years of Frontiers in Cellular Neuroscience: the role of glial cells in schizophrenia and other related disorders.","authors":"Hai-Ying Shen","doi":"10.3389/fncel.2024.1471266","DOIUrl":"https://doi.org/10.3389/fncel.2024.1471266","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389274","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":"The function of <i>Mef2c</i> toward the development of excitatory and inhibitory cortical neurons.","authors":"Claire Ward, Lucas Sjulson, Renata Batista-Brito","doi":"10.3389/fncel.2024.1465821","DOIUrl":"https://doi.org/10.3389/fncel.2024.1465821","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs) are caused by abnormal brain development, leading to altered brain function and affecting cognition, learning, self-control, memory, and emotion. NDDs are often demarcated as discrete entities for diagnosis, but empirical evidence indicates that NDDs share a great deal of overlap, including genetics, core symptoms, and biomarkers. Many NDDs also share a primary sensitive period for disease, specifically the last trimester of pregnancy in humans, which corresponds to the neonatal period in mice. This period is notable for cortical circuit assembly, suggesting that deficits in the establishment of brain connectivity are likely a leading cause of brain dysfunction across different NDDs. Regulators of gene programs that underlie neurodevelopment represent a point of convergence for NDDs. Here, we review how the transcription factor MEF2C, a risk factor for various NDDs, impacts cortical development. Cortical activity requires a precise balance of various types of excitatory and inhibitory neuron types. We use MEF2C loss-of-function as a study case to illustrate how brain dysfunction and altered behavior may derive from the dysfunction of specific cortical circuits at specific developmental times.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396926","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":"Corrigendum: Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1^G93A mice.","authors":"Ana Laura M R Tomiyama, Luciana Politti Cartarozzi, Lilian de Oliveira Coser, Gabriela Bortolança Chiarotto, Alexandre L R Oliveira","doi":"10.3389/fncel.2024.1493884","DOIUrl":"https://doi.org/10.3389/fncel.2024.1493884","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2023.1211486.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389272","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":"The impacts of hypertonic conditions on <i>Drosophila</i> larval cool cells.","authors":"Hua Bai, Trisha Naidu, James B Anderson, Hector Montemayor, Camie Do, Lina Ni","doi":"10.3389/fncel.2024.1347460","DOIUrl":"10.3389/fncel.2024.1347460","url":null,"abstract":"<p><p><i>Drosophila melanogaster</i> exhibits multiple highly sophisticated temperature-sensing systems, enabling its effective response and navigation to temperature changes. Previous research has identified three dorsal organ cool cells (DOCCs) in fly larvae, consisting of two A-type and one B-type cell with distinct calcium dynamics. When subjected to hypertonic conditions, calcium imaging shows that A-type DOCCs maintain their responses to cool temperatures. In contrast, a subset of B-type DOCCs does not exhibit detectable GCaMP baseline signals, and the remaining detectable B-type DOCCs exhibit reduced temperature responses. The activation of both A-type and B-type DOCCs depends on the same members of the ionotropic receptor (IR) family: IR21a, IR93a, and IR25a. A-type DOCCs exhibit a higher somal level of IR93a than B-type DOCCs. Overexpression of <i>Ir93a</i> restores B-type calcium responses to cool temperatures, but not the proportion of B-type cells with a detectable GCaMP baseline, in a hypertonic environment, suggesting a selective role of IR93a in maintaining the temperature responses under hypertonic conditions. Our findings identify a novel function of B-type DOCCs in integrating temperature and tonic stimuli.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389277","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":"Photobiomodulation regulates astrocyte activity and ameliorates scopolamine-induced cognitive behavioral decline.","authors":"Ji On Park, Namgue Hong, Min Young Lee, Jin-Chul Ahn","doi":"10.3389/fncel.2024.1448005","DOIUrl":"10.3389/fncel.2024.1448005","url":null,"abstract":"<p><strong>Introduction: </strong>The pathophysiological mechanism of Alzheimer's disease (AD) has not been clearly identified, and effective treatment methods have not yet been established. Scopolamine causes cholinergic dysfunction in the brain, including the accumulation of amyloid-beta plaques, thereby increasing oxidative stress and neuroinflammation, mimicking AD. Glial cells such as astrocytes have recently been identified as possible biomarkers for AD. Photobiomodulation (PBM) elicits a beneficial biological response in cells and tissues. PBM effects on the central nervous system (CNS) have been widely researched, including effects on astrocyte activity.</p><p><strong>Methods: </strong>In the present study, PBM was performed using light at the near-infrared wavelength of 825 nm. The Morris water maze and Y-maze tests were employed to evaluate cognitive function decline in a scopolamine-induced memory dysfunction model and its improvement with PBM. In addition, alteration of the mitogen-activated protein kinase (MAPK) pathway and immunofluorescence expression levels of active astrocytes were observed in the hippocampus, which is one of the areas affected by AD, to evaluate the mechanism of action of PBM.</p><p><strong>Results: </strong>A reduction in the neuronal cell death in the hippocampus caused by scopolamine was observed with PBM. Moreover, alteration of a MAPK pathway-related marker and changes in glial fibrillary acidic protein (an active astrocyte marker) expression were observed in the PBM-treated group. Finally, significant correlations between functional and histological results were found, validating the results.</p><p><strong>Discussion: </strong>These findings indicate the possibility of behavioral and histological improvement due to PBM in scopolamine-induced CNS alteration, which mimics AD. This improvement could be related to neuroinflammatory modulation and altered astrocyte activity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380468","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":"Glucose metabolism impairment as a hallmark of progressive myoclonus epilepsies: a focus on neuronal ceroid lipofuscinoses.","authors":"Lorenzo Santucci, Sara Bernardi, Rachele Vivarelli, Filippo Maria Santorelli, Maria Marchese","doi":"10.3389/fncel.2024.1445003","DOIUrl":"10.3389/fncel.2024.1445003","url":null,"abstract":"<p><p>Glucose is the brain's main fuel source, used in both energy and molecular production. Impaired glucose metabolism is associated with adult and pediatric neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), GLUT1 deficiency syndrome, and progressive myoclonus epilepsies (PMEs). PMEs, a group of neurological disorders typical of childhood and adolescence, account for 1% of all epileptic diseases in this population worldwide. Diffuse glucose hypometabolism is observed in the brains of patients affected by PMEs such as Lafora disease (LD), dentatorubral-pallidoluysian (DRPLA) atrophy, Unverricht-Lundborg disease (ULD), and myoclonus epilepsy with ragged red fibers (MERRFs). PMEs also include neuronal ceroid lipofuscinoses (NCLs), a subgroup in which lysosomal and autophagy dysfunction leads to progressive loss of vision, brain atrophy, and cognitive decline. We examine the role of impaired glucose metabolism in neurodegenerative diseases, particularly in the NCLs. Our literature review, which includes findings from case reports and animal studies, reveals that glucose hypometabolism is still poorly characterized both <i>in vitro</i> and <i>in vivo</i> in the different NCLs. Better identification of the glucose metabolism pathway impaired in the NCLs may open new avenues for evaluating the therapeutic potential of anti-diabetic agents in this population and thus raise the prospect of a therapeutic approach able to delay or even halt disease progression.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371380","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":"Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition","authors":"Parker J. Ellingson, Yousif O. Shams, Jessica R. Parker, Ronald L. Calabrese, Gennady S. Cymbalyuk","doi":"10.3389/fncel.2024.1395026","DOIUrl":"https://doi.org/10.3389/fncel.2024.1395026","url":null,"abstract":"For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na<jats:sup>+</jats:sup>/K<jats:sup>+</jats:sup> pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260208","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":"Discovery of GJC1 as a prognostic biomarker in glioma cells: insights into its cell-cycle relationship and differential expression in non-neuronal cells","authors":"Xiangtian Ji, Xin Chen, Guozhong Lin, Kaiming Ma, Junhua Yang, Xiaofang Zhao, Suhua Chen, Jun Yang","doi":"10.3389/fncel.2024.1440409","DOIUrl":"https://doi.org/10.3389/fncel.2024.1440409","url":null,"abstract":"BackgroundGliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of <jats:italic>GJC1</jats:italic> in gliomas and explored its relationship with the cell cycle.MethodsRetrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of <jats:italic>GJC1</jats:italic> in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between <jats:italic>GJC1</jats:italic> expression and predicted treatment response across these databases.Results<jats:italic>GJC1</jats:italic> expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. <jats:italic>GJC1</jats:italic> enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, <jats:italic>GJC1</jats:italic> expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more <jats:italic>GJC1</jats:italic> expression than the other subgroups. <jats:italic>GJC1</jats:italic> emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which <jats:italic>GJC1</jats:italic> may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between <jats:italic>GJC1</jats:italic> expression and the sensitivity of multiple anti-cancer drugs.ConclusionThese findings confirmed <jats:italic>GJC1</jats:italic> as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, <jats:italic>GJC1</jats:italic> may be used to predict glioma prognosis and has potential therapeutic value.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260209","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":"Multifaceted neuroprotective approach of Trolox in Alzheimer's disease mouse model: targeting Aβ pathology, neuroinflammation, oxidative stress, and synaptic dysfunction","authors":"Muhammad Tahir, Min Hwa Kang, Tae Ju Park, Jawad Ali, Kyonghwan Choe, Jun Sung Park, Myeong Ok Kim","doi":"10.3389/fncel.2024.1453038","DOIUrl":"https://doi.org/10.3389/fncel.2024.1453038","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aβ<jats:sub>1 − 42</jats:sub>-induced AD mouse model. Aβ<jats:sub>1 − 42</jats:sub> 5μL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and β-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1β (IL-1β), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260207","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}