Cellular and Molecular Neurobiology最新文献

{"title":"The Role of Extracellular Vesicles and Microparticles in Central Nervous System Disorders: Mechanisms, Biomarkers, and Therapeutic Potential.","authors":"Soroush Najdaghi, Delaram Narimani Davani, Hamed Fouladseresht, Narges Ebrahimi, Mark J M Sullman, Marjan Moradi, Nahid Eskandari","doi":"10.1007/s10571-024-01518-w","DOIUrl":"10.1007/s10571-024-01518-w","url":null,"abstract":"<p><p>Microscopic, membranous vesicles known as extracellular vesicles (EVs) have been proposed to play a role in the mechanisms underlying central nervous system (CNS) diseases. EVs are secreted by a variety of cells, including myeloid, endothelial, microglial, oligodendroglial, and mesenchymal stem cells (MSCs). Body fluids such as plasma, urine, and cerebrospinal fluid (CSF) contain microparticles (MPs). The detection of MPs in CSF may indicate genetic or environmental susceptibility to conditions such as schizophrenia, schizoaffective disorder, and bipolar disorder. MPs of different origins can exhibit changes in specific biomarkers at various stages of the disease, aiding in the diagnosis and monitoring of neurological conditions. However, understanding the role and clinical applications of MPs is complicated by challenges such as their isolation and dual roles within the CNS. In this review, we discuss the history, characteristics, and roles of MPs in CNS diseases. We also provide practical insights for future research and highlight the challenges that obscure the therapeutic potential of MPs.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"82"},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Cellular Foundations of Aging of the Brain: Anti-aging Strategies in Alzheimer's Disease.","authors":"Magdalena Dziewa, Magdalena Złotek, Mariola Herbet, Iwona Piątkowska-Chmiel","doi":"10.1007/s10571-024-01514-0","DOIUrl":"10.1007/s10571-024-01514-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a condition characterized by the gradual degeneration of the nervous system that poses significant challenges to cognitive function and overall mental health. Given the increasing global life expectancy, there is an urgent need for effective strategies to prevent and manage Alzheimer's disease, with a particular focus on anti-aging interventions. Recent scientific advancements have unveiled several promising strategies for combating Alzheimer's disease (AD), ranging from lifestyle interventions to cutting-edge pharmacological treatments and therapies targeting the underlying biological processes of aging and AD. Regular physical exercise, cognitive engagement, a balanced diet, and social interaction serve as key pillars in maintaining brain health. At the same time, therapies target key pathological mechanisms of AD, such as amyloid-beta accumulation, tau abnormalities, neuroinflammation, mitochondrial dysfunction, and synaptic loss, offering potential breakthroughs in treatment. Moreover, cutting-edge innovations such as gene therapy, stem cell transplantation, and novel drug delivery systems are emerging as potential game-changers in the fight against AD. This review critically evaluates the latest research on anti-aging interventions and their potential in preventing and treating Alzheimer's disease (AD) by exploring the connections between aging mechanisms and AD pathogenesis. It provides a comprehensive analysis of both well-established and emerging strategies, while also identifying key gaps in current knowledge to guide future research efforts.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"80"},"PeriodicalIF":3.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathic Pain Induced by Spinal Cord Injury from the Glia Perspective and Its Treatment.","authors":"Ying Ye, Xinjin Su, Jun Tang, Chao Zhu","doi":"10.1007/s10571-024-01517-x","DOIUrl":"10.1007/s10571-024-01517-x","url":null,"abstract":"<p><p>Regional neuropathic pain syndromes above, at, or below the site of spinal damage arise after spinal cord injury (SCI) and are believed to entail distinct pathways; nevertheless, they may share shared defective glial systems. Neuropathic pain after SCI is caused by glial cells, ectopic firing of neurons endings and their intra- and extracellular signaling mechanisms. One such mechanism occurs when stimuli that were previously non-noxious become so after the injury. This will exhibit a symptom of allodynia. Another mechanism is the release of substances by glia, which keeps the sensitivity of dorsal horn neurons even in regions distant from the site of injury. Here, we review, the models and identifications of SCI-induced neuropathic pain (SCI-NP), the mechanisms of SCI-NP related to glia, and the treatments of SCI-NP.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"81"},"PeriodicalIF":3.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Photobiomodulation to Modulate Ion Channels in the Nervous System: A Systematic Review.","authors":"Zhixin Zhang, Zhiyu Zhang, Peng Liu, Xinmiao Xue, Chi Zhang, Lili Peng, Weidong Shen, Shiming Yang, Fangyuan Wang","doi":"10.1007/s10571-024-01513-1","DOIUrl":"10.1007/s10571-024-01513-1","url":null,"abstract":"<p><p>Photobiomodulation (PBM) is a safe and effective neurotherapy that modulates cellular pathways by altering cell membrane potentials, leading to beneficial biological effects such as anti-inflammatory and neuroregenerative responses. This review compiles studies from PubMed up to March 2024, investigating the impact of light at wavelengths ranging from 620 to 1270 nm on ion channels. Out of 330 articles screened, 19 met the inclusion criteria. Research indicates that PBM can directly affect various ion channels by influencing neurotransmitter synthesis in neighboring cells, impacting receptors like glutamate and acetylcholine, as well as potassium, sodium channels, and transient receptor potential channels. The diversity of studies hampers a comprehensive meta-analysis for evaluating treatment strategies effectively. This systematic review aims to explore the potential role of optoelectronic signal transduction in PBM, studying the neurobiological mechanisms and therapeutic significance of PBM on ion channels. However, the lack of uniformity in current treatment methods underscores the necessity of establishing standardized and reliable therapeutic approaches.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"79"},"PeriodicalIF":3.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Inflammatory Cascade and Reactive Astrogliosis in Glial Scar Formation Post-spinal Cord Injury.","authors":"Manini Bhatt, Muskan Sharma, Bodhisatwa Das","doi":"10.1007/s10571-024-01519-9","DOIUrl":"10.1007/s10571-024-01519-9","url":null,"abstract":"<p><p>Reactive astrogliosis and inflammation are pathologic hallmarks of spinal cord injury. After injury, dysfunction of glial cells (astrocytes) results in glial scar formation, which limits neuronal regeneration. The blood-spinal cord barrier maintains the structural and functional integrity of the spinal cord and does not allow blood vessel components to leak into the spinal cord microenvironment. After the injury, disruption in the spinal cord barrier causes an imbalance of the immunological microenvironment. This triggers the process of neuroinflammation, facilitated by the actions of microglia, neutrophils, glial cells, and cytokines production. Recent work has revealed two phenotypes of astrocytes, A1 and A2, where A2 has a protective type, and A1 releases neurotoxins, further promoting glial scar formation. Here, we first describe the current understanding of the spinal cord microenvironment, both pre-, and post-injury, and the role of different glial cells in the context of spinal cord injury, which forms the essential update on the cellular and molecular events following injury. We aim to explore in-depth signaling pathways and molecular mediators that trigger astrocyte activation and glial scar formation. This review will discuss the activated signaling pathways in astrocytes and other glial cells and their collaborative role in the development of gliosis through inflammatory responses.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"78"},"PeriodicalIF":3.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rasopathy-Associated Mutation Ptpn11^D61Y has Age-Dependent Effect on Synaptic Vesicle Recycling.","authors":"Debarpan Guhathakurta, Franziska Selzam, Aneta Petrušková, Eva-Maria Weiss, Enes Yağız Akdaş, Carolina Montenegro-Venegas, Martin Zenker, Anna Fejtová","doi":"10.1007/s10571-024-01505-1","DOIUrl":"10.1007/s10571-024-01505-1","url":null,"abstract":"<p><p>Rasopathies are genetic disorders often associated with developmental delay and intellectual disability. Noonan syndrome (NS) is one of the most common Rasopathies, caused by mutations in PTPN11 in more than 50% of cases. In mammalian neurons, PTPN11 controls the trafficking of postsynaptic glutamate receptors. This process is disrupted in neurons expressing PTPN11 variants associated with Rasopathies and is thought to contribute to the cognitive impairments in Noonan syndrome. Recent work revealed presynaptic impairments upon expression of RASopathy-linked PTPN11 variants in Drosophila. However, the presynaptic role of PTPN11 has not yet been addressed in mammals. Here, we investigated membrane trafficking of synaptic vesicles in cultured mouse cortical neurons expressing Rasopathy-associated PTPN11^D61Y variant. We observed a significantly smaller readily releasable and total recycling pool of synaptic vesicles. The drop in synaptic vesicle release competence was accompanied by a decreased rate of SV retrieval. Interestingly, the presynaptic phenotype was evident in mature (DIV21) but not in immature (DIV12) neurons. Thus, our data reveal importance of balanced PTPN11 activity for normal trafficking of neurotransmitter-filled synaptic vesicles in the presynaptic ending of mature neurons.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"77"},"PeriodicalIF":3.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt-5a Signaling Mediates Metaplasticity at Hippocampal CA3-CA1 Synapses in Mice.","authors":"Jorge Parodi, Rodrigo G Mira, Marco Fuenzalida, Waldo Cerpa, Felipe G Serrano, Cheril Tapia-Rojas, Ataulfo Martinez-Torres, Nibaldo C Inestrosa","doi":"10.1007/s10571-024-01512-2","DOIUrl":"10.1007/s10571-024-01512-2","url":null,"abstract":"<p><p>Wnt signaling plays a role in synaptic plasticity, but the specific cellular events and molecular components involved in Wnt signaling-mediated synaptic plasticity are not well defined. Here, we report a change in the threshold required to induce synaptic plasticity that facilitates the induction of long-term potentiation (LTP) and inhibits the induction of long-term depression (LTD) during brief exposure to the noncanonical ligand Wnt-5a. Both effects are related to the metaplastic switch of hippocampal CA3-CA1 synaptic transmission, a complex mechanism underlying the regulation of the threshold required to induce synaptic plasticity and of synaptic efficacy. We observed an early increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) that persisted over time, including after washout. The first phase involves an increase in the fEPSP amplitude that is required to trigger a spontaneous second phase that depends on Jun N-terminal kinase (JNK) and N-methyl D-aspartate receptor (NMDAR) activity. These changes are prevented by treatment with secreted frizzled-related protein 2 (sFRP-2), an endogenous antagonist of Wnt ligands. Here, we demonstrate the contribution of Wnt-5a signaling to a process associated with metaplasticity at CA3-CA1 synapses that favors LTP over LTD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"76"},"PeriodicalIF":3.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal Muscular Atrophy: Current Medications and Re-purposed Drugs.","authors":"Soumyadutta Basak, Nupur Biswas, Jaya Gill, Shashaanka Ashili","doi":"10.1007/s10571-024-01511-3","DOIUrl":"10.1007/s10571-024-01511-3","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is an autosomal recessive genetic neuromuscular disorder that is characterized by gradual muscle weakness and atrophy due to the degeneration of alpha motor neurons that are present on the anterior horn of the spinal cord. Despite the comprehensive investigations conducted by global scientists, effective treatments or interventions remain elusive. The time- and resource-intensive nature of the initial stages of drug research underscores the need for alternate strategies like drug repurposing. This review explores the repurposed drugs that have shown some improvement in treating SMA, including branaplam, riluzole, olesoxime, harmine, and prednisolone. The current strategy for medication repurposing, however, lacks systematicity and frequently depends more on serendipitous discoveries than on organized approaches. To speed up the development of successful therapeutic interventions, it is apparent that a methodical approach targeting the molecular origins of SMA is strictly required.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"75"},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Epistasis and Systems Biology Approaches to Uncover a Pharmacogenomic Map Linked to Pain, Anti-Inflammatory and Immunomodulating Agents (PAIma) in a Healthy Cohort.","authors":"Alireza Sharafshah, Majid Motovali-Bashi, Parvaneh Keshavarz, Kenneth Blum","doi":"10.1007/s10571-024-01504-2","DOIUrl":"10.1007/s10571-024-01504-2","url":null,"abstract":"<p><p>The global public health addiction crisis has been stark, with over 932,400 deaths in the USA and Canada from opioid overdose since 1999-2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), this approach aims to optimize pain management, enhance safety, and reduce addiction risks. This understanding prompted the utilization of multifactor dimensionality reduction (MDR) to explore a range of phenotypes including PGx and gene-gene interactions (GGI) in a healthy cohort, thereby personalizing pain management strategies. The study sampled 100 unrelated healthy Western Iranians and 100 individuals from the 1000 Genome Project. Pre-testing involved searching for PGx annotations (variants associated with drug-gene-diseases) related to pain sensitivity and inflammation using the PharmGKB database, which identified 128 relevant genes. A questionnaire helped select 100 participants who had never used potent opioids but also other psychoactive agents (e.g., nicotine, amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was then employed to analyze these genes in an Iranian cohort. Further analyses included MDR for identifying synergistic gene annotations and GGI for exploring complex gene interactions through the Visualization of Statistical Epistasis Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 annotations across 21 curated pathways. After filtering, 54 significant structural or regulatory variants were identified. This research also highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, Paliperidone, and CYP2D6, which warrant further investigation. This study offers a novel pharmacogenetic framework that could potentially transform opioid prescribing practices to mitigate misuse and enhance personalized pain management. Further validation of these findings from multi countries and ethnic groups could guide clinicians in implementing DNA-based opioid prescribing, aligning treatment more closely with individual genetic profiles.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"74"},"PeriodicalIF":3.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pesticide Exposure and Its Association with Parkinson's Disease: A Case-Control Analysis.","authors":"Ali Samareh, Hossein Pourghadamyari, Mohammad Hadi Nemtollahi, Hossein Ali Ebrahimi Meimand, Mohammad Erfan Norouzmahani, Gholamreza Asadikaram","doi":"10.1007/s10571-024-01501-5","DOIUrl":"10.1007/s10571-024-01501-5","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a complex disorder that arises from genetic and environmental factors. The current investigation endeavors to investigate the role of exposure to organochlorine (OCPs) and organophosphate pesticides (OPPs), recognized as the main environmental elements, in the genesis of PD. In this case-control study, 29 PD patients and 51 healthy subjects were involved. Gas chromatography was performed to measure the serum levels of organochlorine chemicals (2,4-DDT, 4,4-DDT, 2,4-DDE, 4,4-DDE, α-HCH, β-HCH, and γ-HCH). Furthermore, acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (PON-1), and several oxidative stress (OS) markers were assessed. The levels of OCPs in the PD patients were significantly higher than in the control subjects. In addition, AChE activity, arylesterase activity of PON-1, catalase activity, and superoxide dismutase 3 activity in PD patients were significantly less than controls. However, the levels of carbonyl protein, total antioxidant capacity, malondialdehyde, and nitric oxide in PD patients were higher than the controls. The findings of this investigation have indicated that OCPs and OPPs exposure could contribute to the development of Parkinson's disease. This potential linkage could either be established through the direct impact of these pesticides on the nervous system, leading to neurotoxicity, or via an indirect route through the triggering of OS.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"73"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}