Cellular and Molecular Neurobiology最新文献

{"title":"Clinical Insights on Caloric Restriction Mimetics for Mitigating Brain Aging and Related Neurodegeneration.","authors":"Anchal Trisal, Abhishek Kumar Singh","doi":"10.1007/s10571-024-01493-2","DOIUrl":"https://doi.org/10.1007/s10571-024-01493-2","url":null,"abstract":"<p><p>Aging, an inevitable physiological process leading to a progressive decline in bodily functions, has been an abundantly researched domain with studies attempting to slow it down and reduce its debilitating effects. Investigations into the cellular and molecular pathways associated with aging have allowed the formulation of therapeutic strategies. Of these, caloric restriction (CR) has been implicated for its role in promoting healthy aging by modulating key molecular targets like Insulin/IGF-1, mTOR, and sirtuins. However, CR requires dedication and commitment to a strict regimen which poses a difficulty in maintaining consistency. To maneuver around cumbersome diets, Caloric Restriction Mimetics (CRMs) have emerged as promising alternatives by mimicking the beneficial effects of CR. This review elucidates the molecular foundations enabling CRMs like rapamycin, metformin, resveratrol, spermidine, and many more to function as suitable anti-aging molecules. Moreover, it explores clinical trials (retrieved from the clinicaltrials.gov database) aimed at demonstrating the efficacy of CRMs as effective candidates against age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"67"},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459053","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":"Correction: Upregulation of Glutamatergic Receptors in Hippocampus and Locomotor Hyperactivity in Aged Spontaneous Hypertensive Rat.","authors":"Patrick Szu-Ying Yen, Yen-Chin Liu, Chun-Hsien Chu, Shiou-Lan Chen","doi":"10.1007/s10571-024-01498-x","DOIUrl":"https://doi.org/10.1007/s10571-024-01498-x","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"66"},"PeriodicalIF":3.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Single-Cell RNA Sequencing and Spatial Transcriptomics for Central Nervous System Disease.","authors":"Yuan Zhang, Teng Li, Guangtian Wang, Yabin Ma","doi":"10.1007/s10571-024-01499-w","DOIUrl":"https://doi.org/10.1007/s10571-024-01499-w","url":null,"abstract":"<p><p>The incidence of central nervous system (CNS) disease has persistently increased over the last several years. There is an urgent need for effective methods to improve the cure rates of CNS disease. However, the precise molecular basis underlying the development and progression of major CNS diseases remains elusive. A complete molecular map will contribute to research on CNS disease treatment strategies. Emerging technologies such as single-cell RNA sequencing (scRNA-seq) and Spatial Transcriptomics (ST) are potent tools for exploring the molecular complexity, cell heterogeneity, and functional specificity of CNS disease. scRNA-seq and ST can provide insights into the disease at cellular and spatial transcription levels. This review presents a survey of scRNA-seq and ST studies on CNS diseases, such as chronic neurodegenerative diseases, acute CNS injuries, and others. These studies offer novel perspectives in treating and diagnosing CNS diseases by discovering new cell types or subtypes associated with the disease, proposing new pathophysiological mechanisms, uncovering novel therapeutic targets, and identifying putative biomarkers.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"65"},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459051","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":"Gut-Brain Axis and Neuroinflammation: The Role of Gut Permeability and the Kynurenine Pathway in Neurological Disorders.","authors":"Rowan Kearns","doi":"10.1007/s10571-024-01496-z","DOIUrl":"10.1007/s10571-024-01496-z","url":null,"abstract":"<p><p>The increasing prevalence of neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis presents a significant global health challenge. Despite extensive research, the precise mechanisms underlying these conditions remain elusive, with current treatments primarily addressing symptoms rather than root causes. Emerging evidence suggests that gut permeability and the kynurenine pathway are involved in the pathogenesis of these neurological conditions, offering promising targets for novel therapeutic and preventive strategies. Gut permeability refers to the intestinal lining's ability to selectively allow essential nutrients into the bloodstream while blocking harmful substances. Various factors, including poor diet, stress, infections, and genetic predispositions, can compromise gut integrity, leading to increased permeability. This condition facilitates the translocation of toxins and bacteria into systemic circulation, triggering widespread inflammation that impacts neurological health via the gut-brain axis. The gut-brain axis (GBA) is a complex communication network between the gut and the central nervous system. Dysbiosis, an imbalance in the gut microbiota, can increase gut permeability and systemic inflammation, exacerbating neuroinflammation-a key factor in neurological disorders. The kynurenine pathway, the primary route for tryptophan metabolism, is significantly implicated in this process. Dysregulation of the kynurenine pathway in the context of inflammation leads to the production of neurotoxic metabolites, such as quinolinic acid, which contribute to neuronal damage and the progression of neurological disorders. This narrative review highlights the potential and progress in understanding these mechanisms. Interventions targeting the kynurenine pathway and maintaining a balanced gut microbiota through diet, probiotics, and lifestyle modifications show promise in reducing neuroinflammation and supporting brain health. In addition, pharmacological approaches aimed at modulating the kynurenine pathway directly, such as inhibitors of indoleamine 2,3-dioxygenase, offer potential avenues for new treatments. Understanding and targeting these interconnected pathways are crucial for developing effective strategies to prevent and manage neurological disorders.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"64"},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388375","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":"Correction: Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension.","authors":"Mia Langbøl, Arevak Saruhanian, Sarkis Saruhanian, Daniel Tiedemann, Thisayini Baskaran, Rupali Vohra, Amalie Santaolalla Rives, José Moreira, Verena Prokosch, Hanhan Liu, Jan-Wilm Lackmann, Stefan Müller, Claus Henrik Nielsen, Miriam Kolko, Jens Rovelt","doi":"10.1007/s10571-024-01500-6","DOIUrl":"10.1007/s10571-024-01500-6","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"63"},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371095","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":"Research Progress on the Effects of Different Exercise Modes on the Secretion of Exerkines After Spinal Cord Injury.","authors":"Qianxi Li, Chenyu Li, Xin Zhang","doi":"10.1007/s10571-024-01497-y","DOIUrl":"10.1007/s10571-024-01497-y","url":null,"abstract":"<p><p>Exercise training is a conventional treatment strategy throughout the entire treatment process for patients with spinal cord injury (SCI). Currently, exercise modalities for SCI patients primarily include aerobic exercise, endurance training, strength training, high-intensity interval training, and mind-body exercises. These exercises play a positive role in enhancing skeletal muscle function, inducing neuroprotection and regeneration, thereby influencing neural plasticity, reducing limb spasticity, and improving motor function and daily living abilities in SCI patients. However, the mechanism by which exercise training promotes functional recovery after SCI is still unclear, and there is no consensus on a unified and standardized exercise treatment plan. Different exercise methods may bring different benefits. After SCI, patients' physical activity levels decrease significantly due to factors such as motor dysfunction, which may be a key factor affecting changes in exerkines. The changes in exerkines of SCI patients caused by exercise training are an important and highly relevant and visual evaluation index, which may provide a new research direction for revealing the intrinsic mechanism by which exercise promotes functional recovery after SCI. Therefore, this article summarizes the changes in the expression of common exerkines (neurotrophic factors, inflammatory factors, myokines, bioactive peptides) after SCI, and intends to analyze the impact and role of different exercise methods on functional recovery after SCI from the perspective of exerkines mechanism. We hope to provide theoretical basis and data support for scientific exercise treatment programs after SCI.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"62"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342416","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":"Correction: Upregulation of miR-107 Inhibits Glioma Angiogenesis and VEGF Expression","authors":"Lei Chen, Zong-yang Li, Sui-yi Xu, Xie-jun Zhang, Yuan Zhang, Kun Luo, Wei-ping Li","doi":"10.1007/s10571-024-01495-0","DOIUrl":"https://doi.org/10.1007/s10571-024-01495-0","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"3 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactobacilli Cell-Free Supernatants Modulate Inflammation and Oxidative Stress in Human Microglia via NRF2-SOD1 Signaling","authors":"Mariagiovanna Di Chiano, Maria Teresa Rocchetti, Giuseppe Spano, Pasquale Russo, Caterina Allegretta, Giampaolo Milior, Raffaella Maria Gadaleta, Fabio Sallustio, Paola Pontrelli, Loreto Gesualdo, Carlo Avolio, Daniela Fiocco, Anna Gallone","doi":"10.1007/s10571-024-01494-1","DOIUrl":"https://doi.org/10.1007/s10571-024-01494-1","url":null,"abstract":"<p>Microglia are macrophage cells residing in the brain, where they exert a key role in neuronal protection. Through the gut–brain axis, metabolites produced by gut commensal microbes can influence brain functions, including microglial activity. The nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the oxidative stress response in microglia, controlling the expression of cytoprotective genes. Lactobacilli-derived cell-free supernatants (CFSs) are postbiotics that have shown antioxidant and immunomodulatory effects in several in vitro and in vivo studies. This study aimed to explore the effects of lactobacilli CFSs on modulating microglial responses against oxidative stress and inflammation. HMC3 microglia were exposed to lipopolysaccaride (LPS), as an inflammatory trigger, before and after administration of CFSs from three human gut probiotic species. The NRF2 nuclear protein activation and the expression of NRF2-controlled antioxidant genes were investigated by immunoassay and quantitative RT-PCR, respectively. Furthermore, the level of pro- and anti-inflammatory cytokines was evaluated by immunoassay. All CFSs induced a significant increase of NRF2 nuclear activity in basal conditions and upon inflammation. The transcription of antioxidant genes, namely heme oxygenase 1, superoxide dismutase (SOD), glutathione-S transferase, glutathione peroxidase, and catalase also increased, especially after inflammatory stimulus. Besides, higher SOD1 activity was detected relative to inflamed microglia. In addition, CFSs pre-treatment of microglia attenuated pro-inflammatory TNF-α levels while increasing anti-inflammatory IL-10 levels. These findings confirmed that gut microorganisms’ metabolites can play a relevant role in adjuvating the microglia cellular response against neuroinflammation and oxidative stress, which are known to cause neurodegenerative diseases.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><p>Gut-brain crosstalk: molecular point of view. Metabolites contained in the supernatant derived from Lactobacilli can cross the gut barrier and reach the central nervous system, where they are taken up by microglial cells. They induce the activation of the NRF2 pathway and the production of inflammatory mediators. This interaction attenuates two important events: oxidation (with high levels of NRF2) and inflammation (with high levels of IL-10 and low levels of TNF-α).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"119 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension.","authors":"Mia Langbøl, Arevak Saruhanian, Sarkis Saruhanian, Daniel Tiedemann, Thisayini Baskaran, Rupali Vohra, Amalie Santaolalla Rives, José Moreira, Verena Prokosch, Hanhan Liu, Jan-Wilm Lackmann, Stefan Müller, Claus Henrik Nielsen, Miriam Kolko, Jens Rovelt","doi":"10.1007/s10571-024-01492-3","DOIUrl":"10.1007/s10571-024-01492-3","url":null,"abstract":"<p><p>Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before (\"baseline\"), during (\"hypoxia\"), and after hypoxia (\"recovery\"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"59"},"PeriodicalIF":3.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987486","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":"Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.","authors":"Chao Cui, Xue Jiang, Yumei Wang, Chao Li, Zhaochen Lin, Youzhen Wei, Qingbin Ni","doi":"10.1007/s10571-024-01491-4","DOIUrl":"10.1007/s10571-024-01491-4","url":null,"abstract":"<p><p>This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"58"},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892932","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}