Frontiers in Cellular Neuroscience最新文献

{"title":"Association between cognitive functioning and microbiota-gut-brain axis mediators in a memory clinic population.","authors":"Claudio Singh Solorzano, Cristina Festari, Peppino Mirabelli, Elisa Mombelli, Luigi Coppola, Delia Luongo, Daniele Naviglio, Andrea Soricelli, Giulia Quattrini, Marco Salvatore, Michela Pievani, Annamaria Cattaneo, Giovanni B Frisoni, Moira Marizzoni","doi":"10.3389/fncel.2025.1550333","DOIUrl":"10.3389/fncel.2025.1550333","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1550333"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718220","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":"Translational profiling reveals novel gene expression changes in the direct and indirect pathways in a mouse model of levodopa induced dyskinesia.","authors":"Sabika Jafri, Mahdi Ghani, Natalie Stickle, Carl Virtanen, Lili-Naz Hazrati, Naomi P Visanji","doi":"10.3389/fncel.2024.1477511","DOIUrl":"10.3389/fncel.2024.1477511","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular mechanisms underlying L-dihydroxyphenylalanine (LDOPA) induced dyskinesia in Parkinson's disease are poorly understood. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively isolate RNA from either DRD1A expressing striatonigral, or DRD2 expressing striatopallidal medium spiny neurons (MSNs) of the direct and indirect pathways respectively, to study changes in translational gene expression following repeated LDOPA treatment.</p><p><strong>Methods: </strong>6-OHDA lesioned DRD1A and DRD2 BacTRAP mice were treated with either saline or LDOPA bi-daily for 21 days over which time they developed abnormal involuntary movements reminiscent of dyskinesia. On day 22, all animals received LDOPA 40min prior to sacrifice. The striatum of the lesioned hemisphere was dissected and subject to TRAP. Extracted ribosomal RNA was amplified, purified, and gene expression was quantified using microarray.</p><p><strong>Results: </strong>One hundred ninety-five significantly varying transcripts were identified among the four treatment groups. Pathway analysis revealed an overrepresentation of calcium signaling and long-term potentiation in the DRD1A expressing MSNs of the direct pathway, with significant involvement of long-term depression in the DRD2 expressing MSNs of the indirect pathway following chronic treatment with LDOPA. Several MAPK associated genes (<i>NR4A1, GADD45G, STMN1, FOS</i>, and <i>DUSP1</i>) differentiated the direct and indirect pathways following both acute and chronic LDOPA treatment. However, the MAPK pathway activator <i>PAK1</i> was downregulated in the indirect pathway and upregulated in the direct pathway, strongly suggesting a role for <i>PAK1</i> in regulating the opposing effects of LDOPA on these two pathways in dyskinesia.</p><p><strong>Discussion: </strong>Future studies will assess the potential of targeting these genes and pathways to prevent the development of LDOPA-induced dyskinesia.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1477511"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718206","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":"Characterize neuronal responses to natural movies in the mouse superior colliculus.","authors":"Ya-Tang Li","doi":"10.3389/fncel.2025.1558504","DOIUrl":"10.3389/fncel.2025.1558504","url":null,"abstract":"<p><p>While artificial stimuli have been widely used in visual neuroscience and have significantly advanced our understanding of visual processing, they differ dramatically from the natural scenes that animals encounter in the wild. How natural stimuli are encoded in the superior colliculus (SC) and how neuronal responses to artificial and natural stimuli are related remain poorly understood. Here I applied two-photon calcium imaging to record neuronal activity in the mouse superficial SC in response to natural movies. An unsupervised learning algorithm grouped recorded neurons into 16 clusters based on their response patterns. Each cluster exhibited distinct temporal profiles, which arose from differences in both receptive field coverage and how neurons encode local visual features. Interestingly, I found a strong correlation between neuronal responses to natural movies and functional properties previously characterized using artificial stimuli. This suggests that the SC maintains a stable neural representation of visual information that is largely independent of the types of visual stimuli. Furthermore, neuronal responses to natural movies varied with depth within the superficial SC and across genetically defined neuronal types. These findings bridge the gap between our understanding of responses to artificial and natural stimuli, providing new insights into visual processing in the SC.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1558504"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708220","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":"Thinning of originally-existing, mature myelin represents a nondestructive form of myelin loss in the adult CNS.","authors":"Min Li Lin, Wensheng Lin","doi":"10.3389/fncel.2025.1565913","DOIUrl":"10.3389/fncel.2025.1565913","url":null,"abstract":"<p><p>The main function of oligodendrocytes is to assemble and maintain myelin that wraps and insulates axons in the central nervous system (CNS). Traditionally, myelin structure, particularly its thickness, was believed to remain remarkably stable in adulthood (including early and middle adulthood, but not late adulthood or aging). However, emerging evidence reveals that the thickness of originally-existing, mature myelin (OEM) can undergo dynamic changes in the adult CNS. This overview highlights recent findings on the alteration of OEM thickness in the adult CNS, explores the underlying mechanisms, and proposes that progressive thinning of OEM represents a novel, nondestructive form of myelin loss in myelin disorders of the CNS.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1565913"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709198","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: The role of inflammation in neurodegenerative and psychiatric disorders.","authors":"Dirk M Hermann, Mingyue Zhang, Anfei Huang, Zenghui Teng","doi":"10.3389/fncel.2025.1574274","DOIUrl":"10.3389/fncel.2025.1574274","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1574274"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708504","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":"Riboflavin transporter deficiency: <i>AAV9-SLC52A2</i> gene therapy as a new therapeutic strategy.","authors":"Cecilia Mei, Valentina Magliocca, Xin Chen, Keith Massey, Anai Gonzalez-Cordero, Steven J Gray, Marco Tartaglia, Enrico Silvio Bertini, Stefania Corti, Claudia Compagnucci","doi":"10.3389/fncel.2025.1523773","DOIUrl":"10.3389/fncel.2025.1523773","url":null,"abstract":"<p><p>Riboflavin transporter deficiency syndrome (RTD) is a rare childhood-onset neurodegenerative disorder caused by mutations in <i>SLC52A2</i> and <i>SLC52A3</i> genes, encoding the riboflavin (RF) transporters hRFVT2 and hRFVT3. In the present study we focused on RTD Type 2, which is due to variants in <i>SLC52A2</i> gene. There is no cure for RTD patients and, although studies have reported clinical improvements with administration of RF, an effective treatment is still unavailable. Here we tested gene augmentation therapy on RTD type 2 patient-derived motoneurons using an adeno-associated viral vector 2/9 (AAV9) carrying the human codon optimized <i>SLC52A2</i> cDNA. We optimized the <i>in vitro</i> transduction of motoneurons using sialidase treatment. Treated RTD motoneurons showed a significant increase in neurite's length when compared to untreated samples demonstrating that AAV9-SLC52A2 gene therapy can rescue RTD motoneurons. This leads the path towards <i>in vivo</i> studies offering a potential treatment for RTD patients.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1523773"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709177","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":"PTEN: a new dawn in Parkinson's disease treatment.","authors":"Xinghuang Yang, Tianqi Liu, Hong Cheng","doi":"10.3389/fncel.2025.1497555","DOIUrl":"10.3389/fncel.2025.1497555","url":null,"abstract":"<p><p>In recent years, the study of phosphatase and tension homolog (PTEN) has gradually become a research hotspot. As an important oncogene, the role of PTEN in cancer has long been widely recognized and intensively studied, but it has been relatively less studied in other diseases. Parkinson's disease (PD) is a neurodegenerative refractory disease commonly observed in middle-aged and elderly individuals. The etiology and pathogenesis of PD are numerous, complex, and incompletely understood. With the continuous deepening of research, numerous studies have proven that PTEN is related to the occurrence of PD. In this review, we discuss the relationship between PTEN and PD through the phosphorylation and ubiquitination of PTEN and other possible regulatory mechanisms, including the role of RNA molecules, exosomes, transcriptional regulation, chemical modification, and subtype variation, with the aim of clarifying the regulatory role of PTEN in PD and better elucidating its pathogenesis. Finally, we summarize the shortcomings of PTEN in PD research and highlight the great potential of its future application in PD clinical treatment. These findings provide research ideas and new perspectives for the possible use of PTEN as a PD therapeutic target for targeted drug development and clinical application in the future.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1497555"},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700079","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":"Paving the way for better ototoxicity assessments in cisplatin therapy using more reliable animal models.","authors":"Vijayprakash Manickam, Marisa Zallocchi","doi":"10.3389/fncel.2025.1552051","DOIUrl":"10.3389/fncel.2025.1552051","url":null,"abstract":"<p><p>Cisplatin-induced hearing loss is a common and irreversible side effect affecting a significant proportion of cancer patients. While various strategies to mitigate this toxicity have been explored, there remains a critical need for effective treatments. A major challenge in developing new therapies is the lack of reliable animal models that accurately replicate the clinical use of cisplatin in humans, which typically involves multiple cycles of low-dose administration. Traditional models using high doses of cisplatin have resulted in high mortality and variable hearing loss, complicating the assessment of potential treatments. To address this, a multi-cycle model using lower cisplatin doses in mice was developed, providing hearing loss without mortality. However, variability in outcomes across different research groups persisted. In the present study, we optimize the multi-cycle model of cisplatin-induced ototoxicity by using clinical-grade cisplatin rather than laboratory-grade formulations. The use of clinical cisplatin ensures greater consistency, reliability, and relevance to human treatment protocols, as it adheres to the rigorous quality standards required for patient use. This new administration protocol will minimize variability across research laboratories and more accurately mimic the dosing regimens typically administered to cancer patients. Additionally, we have enhanced a zebrafish model for high-throughput screening of potential therapeutics, further improving the consistency of results. These improvements to the animal models are critical for accelerating the discovery and testing of therapies to prevent cisplatin-induced hearing loss, supporting the development of effective treatments for cancer patients undergoing cisplatin chemotherapy.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1552051"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663101","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":"Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus.","authors":"Hao Wen, Nagisa Sada, Tsuyoshi Inoue","doi":"10.3389/fncel.2025.1551700","DOIUrl":"10.3389/fncel.2025.1551700","url":null,"abstract":"<p><p>The ketogenic diet increases ketone bodies (β-hydroxybutyrate and acetoacetate) in the brain, and ameliorates epileptic seizures <i>in vivo</i>. However, ketone bodies exert weak or no effects on electrical activity in rodent hippocampal slices. Especially, it remains unclear what kinds of conditions are required to strengthen the actions of ketone bodies in hippocampal slices. In the present study, we examined the effects of acetoacetate on hippocampal pyramidal cells in normal slices and epileptiform slices of mice. By using patch-clamp recordings from CA1 pyramidal cells, we first confirmed that acetoacetate did not change the membrane potentials and intrinsic properties of pyramidal cells in normal slices. However, we found that acetoacetate weakened spontaneous epileptiform bursts in pyramidal cells of epileptiform slices, which were acutely induced by applying convulsants to normal slices. Interestingly, acetoacetate did not change the frequency of the epileptiform bursts, but attenuated individual epileptiform bursts. We finally examined the effects of acetoacetate on excitatory synaptic barrages during epileptiform activity, and found that acetoacetate weakened epileptiform bursts by reducing synchronous synaptic inputs. These results show that acetoacetate attenuated neuronal bursts in epileptiform slices, but did not affect neuronal activity in normal slices, which leads to seizure-selective actions of ketone bodies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1551700"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663100","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 role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms.","authors":"Xuan-Yan Ding, Jean de Dieu Habimana, Zhi-Yuan Li","doi":"10.3389/fncel.2025.1547495","DOIUrl":"10.3389/fncel.2025.1547495","url":null,"abstract":"<p><p>As a transmembrane protein, DPP6 modulates the function and properties of ion channels, playing a crucial role in various tissues, particularly in the brain. DPP6 interacts with potassium channel Kv4.2 (KCND2), enhancing its membrane expression and channel kinetics. Potassium ion channels are critical in progressing action potential formation and synaptic plasticity. Therefore, dysfunction of DPP6 can lead to significant health consequences. Abnormal DPP6 expression has been identified in several diseases, such as amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), spinal bulbar muscular atrophy (SBMA), and idiopathic ventricular fibrillation. Recent research has indicated a connection between DPP6 and Alzheimer's disease as well. The most common symptoms resulting from DPP6 dysregulation are mental deficiency and muscle wastage. Notably, these symptoms do not always occur at the same time. Besides genetic factors, environmental factors also undoubtedly play a role in diseases related to DPP6 dysregulation. However, it remains unclear how the expression of DPP6 gets regulated. This review aims to summarize the associations between DPP6 and neurological diseases, offering insights as well as proposing hypotheses to elucidate the underlying mechanisms of DPP6 dysregulation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1547495"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663104","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}