Frontiers in Molecular Neuroscience最新文献

{"title":"Corrigendum: Differential timing of mitochondrial activation in rat dorsal striatum induced by procedural learning and swimming.","authors":"Rogelio Pegueros-Maldonado, Antonio Fuentes-Ibañez, Mónica M Monroy, Oscar A Gutiérrez, Norma Serafín, Santiago M Pech-Pool, Mauricio Díaz-Muñoz, Gina L Quirarte","doi":"10.3389/fnmol.2025.1586135","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1586135","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnmol.2024.1495027.].</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1586135"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779728","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":"Elevated propionate and its association with neurological dysfunctions in propionic acidemia.","authors":"Xiaoxin Chen, Qing Cheng, Guo-Fang Zhang","doi":"10.3389/fnmol.2025.1499376","DOIUrl":"10.3389/fnmol.2025.1499376","url":null,"abstract":"<p><p>Propionate, a short-chain fatty acid (SCFA), has recently attracted attention for its various health benefits. However, elevated levels of propionate in certain pathological conditions can have adverse effects. Propionic acidemia (PA) is a rare metabolic disorder caused by mutations in the propionyl-CoA carboxylase (PCC) gene (<i>PCCA</i> or <i>PCCB</i>), leading to reduced PCC activity and impaired propionyl-CoA metabolism. This metabolic block at the PCC-mediated step results in the accumulation of propionyl-CoA and its metabolites, including propionate, contributing to various complications, such as neurological dysfunction, in patients with PA. This review examines propionate synthesis, its physiological role, its metabolism in healthy individuals and those with PA, and the pathological link between elevated propionate levels and neurological dysfunctions in PA patients. A deeper understanding of propionate metabolism under both normal and pathological conditions will help clarify the full spectrum of its metabolic effects.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1499376"},"PeriodicalIF":3.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772140","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":"Impact of GABA and nutritional supplements on neurochemical biomarkers in autism: a PPA rodent model study.","authors":"Altaf N Alabdali, Abir Ben Bacha, Mona Alonazi, Sameera Abuaish, Ahmad Almotairi, Laila Al-Ayadhi, Afaf K El-Ansary","doi":"10.3389/fnmol.2025.1553438","DOIUrl":"10.3389/fnmol.2025.1553438","url":null,"abstract":"<p><strong>Background/objectives: </strong>Autism spectrum disorder (ASD) is associated with excitatory-inhibitory imbalance and oxidative stress. GABA, an inhibitory neurotransmitter, and related nutritional therapies are promising in restoring these imbalances. GABAergic deficits and glutamate excitotoxicity are two essential signaling pathways that could be addressed to treat autism, thus medications targeting these pathways are critical for treating behavioral symptoms. In a rat model of autism produced by propionic acid (PPA), this study assessed the effects of GABA supplementation and combined nutritional therapy (probiotics, vitamin D3) and <i>β</i>-lactam as an activator of glutamate transporter.</p><p><strong>Methods: </strong>Sixty rats were randomly assigned into six groups: Group I (Control), Group II (PPA-treated), Group III (Control-GABA), Group IV (Control-Combination), Group V (PPA-GABA), and Group VI (PPA-Combination). Social behavior was evaluated using the three-chamber test. Selected biochemical variables related to oxidative stress (GST, Catalase, Lipid peroxides, GSH and Vitamin C), GABA and glutamate signaling (EAAT2, KCC2, NKCC1, GABA, VD3, Glutamate and GABRA5) were measured in the brain homogenates of the six groups. The hippocampus was examined histopathologically to assess cellular integrity.</p><p><strong>Results: </strong>The obtained data revealed that PPA treatment caused significant oxidative stress and neurotransmitter imbalances, characterized by reduced GABA and elevated glutamate levels. GABA supplementation alone produced moderate benefits in biochemical and behavioral markers, but combined therapy considerably restored GABA levels, reduced oxidative stress, and enhanced social interaction behaviors. Histopathology revealed that combination therapy mitigated neurodegenerative changes induced by PPA, preserving hippocampal cellular structure.</p><p><strong>Conclusion: </strong>This study demonstrated that combined therapy (GABA, probiotics, vitamin D3, and <i>β</i>-lactam) were more effective than GABA alone in enhancing neurochemical balance and lowering oxidative stress in a PPA-induced mouse model of autism, indicating promise for treating symptoms.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1553438"},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763817","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":"Retraction: Assessment of expression of regulatory T cell differentiation genes in autism spectrum disorder.","authors":"","doi":"10.3389/fnmol.2025.1586805","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1586805","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fnmol.2022.939224.].</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1586805"},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752255","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 CB1R of mPFC is involved in anxiety-like behavior induced by 0.8/2.65 GHz dual-frequency electromagnetic radiation.","authors":"Bin Sun, Teng Xue, An-Ning Gao, Xin-Yu Wang, Shuang Wu, Xiao-Man Liu, Li-Hui Zhang, Meng-Hua Li, Dong-Fang Zou, Yan Gao, Chang-Zhen Wang","doi":"10.3389/fnmol.2025.1534324","DOIUrl":"10.3389/fnmol.2025.1534324","url":null,"abstract":"<p><p>As mobile phones and communication base stations become more widespread, concerns have arisen regarding the potential risks of environmental exposure to multi-frequency electromagnetic radiation (EMR) and its effects on mental health. To address these concerns, our study established a dual-frequency EMR mouse model at 0.8/2.65 GHz to explore potential molecular mechanisms and intervention targets. Our results revealed that exposure to this dual-frequency EMR significantly induced anxiety-like behavior in mice. Molecular experiments further showed a significant decrease in cannabinoid receptor type 1 (CB1R) levels in the medial prefrontal cortex (mPFC) of the mice, along with a notable reduction in the endogenous cannabinoids 2-arachidonoylglycerol and anandamide. This led to a downregulation of the entire endocannabinoid system (ECS). Additional confirmation was obtained by overexpressing and knocking down CB1R in the mPFC. We found that increasing mPFC CB1R levels could effectively reduce anxiety-like behavior, while decreasing mPFC CB1R levels exacerbated it. Furthermore, we found dual-frequency EMR induced the change of ECS in the basolateral amygdala (BLA). Notably, female mice exhibited similar behavioral phenotypes and molecular mechanisms in response to dual-frequency EMR. In summary, our study demonstrates that anxiety induced by dual-frequency EMR is closely linked to the function of the ECS in the mPFC and BLA, and that CB1R expression in the mPFC plays a significant role in modulating emotional behavior in mice.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1534324"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718534","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: Molecular pathology, biomarkers and therapeutics of brain tumor and neurodegenerative disease.","authors":"Junhui Wang","doi":"10.3389/fnmol.2025.1584157","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1584157","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1584157"},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709525","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: Mechanisms of auditory development, maintenance, damage, and protection.","authors":"Ruosha Lai, Lihua Li, Su-Hua Sha","doi":"10.3389/fnmol.2025.1580793","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1580793","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1580793"},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709545","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: Editors' showcase: neuroplasticity and development.","authors":"Giovanni Cirillo, Michele Papa","doi":"10.3389/fnmol.2025.1558715","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1558715","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1558715"},"PeriodicalIF":3.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669631","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":"Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.","authors":"Elaine K Hebda-Bauer, Megan H Hagenauer, Daniel B Munro, Peter Blandino, Fan Meng, Keiko Arakawa, John D H Stead, Apurva S Chitre, A Bilge Ozel, Pejman Mohammadi, Stanley J Watson, Shelly B Flagel, Jun Li, Abraham A Palmer, Huda Akil","doi":"10.3389/fnmol.2025.1469467","DOIUrl":"10.3389/fnmol.2025.1469467","url":null,"abstract":"<p><p>Externalizing and internalizing behavioral tendencies underlie many psychiatric and substance use disorders. These tendencies are associated with differences in temperament that emerge early in development via the interplay of genetic and environmental factors. To better understand the neurobiology of temperament, we have selectively bred rats for generations to produce two lines with highly divergent behavior: bred Low Responders (bLRs) are highly inhibited and anxious in novel environments, whereas bred High Responders (bHRs) are highly exploratory, sensation-seeking, and prone to drug-seeking behavior. Recently, we delineated these heritable differences by intercrossing bHRs and bLRs (F₀-F₁-F₂) to produce a heterogeneous F₂ sample with well-characterized lineage and behavior (exploratory locomotion, anxiety-like behavior, Pavlovian conditioning). The identified genetic loci encompassed variants that could influence behavior via many mechanisms, including proximal effects on gene expression. Here we measured gene expression in male and female F₀s (<i>n</i> = 12 bHRs, 12 bLRs) and in a large sample of heterogeneous F₂s (<i>n</i> = 250) using hippocampal RNA-Seq. This enabled triangulation of behavior with both genetic and functional genomic data to implicate specific genes and biological pathways. Our results show that bHR/bLR differential gene expression is robust, surpassing sex differences in expression, and predicts expression associated with F₂ behavior. In F₀ and F₂ samples, gene sets related to growth/proliferation are upregulated with bHR-like behavior, whereas gene sets related to mitochondrial function, oxidative stress, and microglial activation are upregulated with bLR-like behavior. Integrating our F₂ RNA-Seq data with previously-collected whole genome sequencing data identified genes with hippocampal expression correlated with proximal genetic variation (<i>cis</i>-expression quantitative trait loci or <i>cis</i>-eQTLs). These <i>cis</i>-eQTLs successfully predict bHR/bLR differential gene expression based on F₀ genotype. Sixteen of these genes are associated with <i>cis</i>-eQTLs colocalized within loci we previously linked to behavior and are strong candidates for mediating the influence of genetic variation on behavioral temperament. Eight of these genes are related to bioenergetics. Convergence between our study and others targeting similar behavioral traits revealed five more genes consistently related to temperament. Overall, our results implicate hippocampal bioenergetic regulation of oxidative stress, microglial activation, and growth-related processes in shaping behavioral temperament, thereby modulating vulnerability to psychiatric and addictive disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1469467"},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656794","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":"Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.","authors":"Melissa J Alldred, Kyrillos W Ibrahim, Harshitha Pidikiti, Sang Han Lee, Adriana Heguy, Gabriela Chiosis, Elliott J Mufson, Grace E Stutzmann, Stephen D Ginsberg","doi":"10.3389/fnmol.2025.1546375","DOIUrl":"10.3389/fnmol.2025.1546375","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals with Down syndrome (DS) exhibit neurological deficits throughout life including the development of in Alzheimer's disease (AD) pathology and cognitive impairment. At the cellular level, dysregulation in neuronal gene expression is observed in postmortem human brain and mouse models of DS/AD. To date, RNA-sequencing (RNA-seq) analysis of hippocampal neuronal gene expression including the characterization of discrete circuit-based connectivity in DS remains a major knowledge gap. We postulate that spatially characterized hippocampal neurons display unique gene expression patterns due, in part, to dysfunction of the integrity of intrinsic circuitry.</p><p><strong>Methods: </strong>We combined laser capture microdissection to microisolate individual neuron populations with single population RNA-seq analysis to determine gene expression analysis of CA1 and CA3 pyramidal neurons and dentate gyrus granule cells located in the hippocampus, a region critical for learning, memory, and synaptic activity.</p><p><strong>Results: </strong>The hippocampus exhibits age-dependent neurodegeneration beginning at ~6 months of age in the Ts65Dn mouse model of DS/AD. Each population of excitatory hippocampal neurons exhibited unique gene expression alterations in Ts65Dn mice. Bioinformatic inquiry revealed unique vulnerabilities and differences with mechanistic implications coinciding with onset of degeneration in this model of DS/AD.</p><p><strong>Conclusions: </strong>These cell-type specific vulnerabilities may underlie degenerative endophenotypes suggesting precision medicine targeting of individual populations of neurons for rational therapeutic development.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1546375"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614569","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}