Cellular and Molecular Neurobiology最新文献

{"title":"Aging and MPTP Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra.","authors":"P L Abhilash, Upasna Bharti, Santhosh Kumar Rashmi, Mariamma Philip, T R Raju, Bindu M Kutty, B K Chandrasekhar Sagar, Phalguni Anand Alladi","doi":"10.1007/s10571-024-01528-8","DOIUrl":"10.1007/s10571-024-01528-8","url":null,"abstract":"<p><p>Both astroglia and microglia show region-specific distribution in CNS and often maladapt to age-associated alterations within their niche. Studies on autopsied substantia nigra (SN) of Parkinson's disease (PD) patients and experimental models propose gliosis as a trigger for neuronal loss. Epidemiological studies propose an ethnic bias in PD prevalence, since Caucasians are more susceptible than non-whites. Similarly, different mice strains are variably sensitive to MPTP. We had earlier likened divergent MPTP sensitivity of C57BL/6 J and CD-1 mice with differential susceptibility to PD, based on the numbers of SN neurons. We examined whether the variability was incumbent to inter-strain differences in glial features of male C57BL/6 J and CD-1 mice. Stereological counts showed relatively more microglia and fewer astrocytes in the SN of normal C57BL/6 J mice, suggesting persistence of an immune-vigilant state. MPTP-induced microgliosis and astrogliosis in both strains suggest their involvement in pathogenesis. ELISA of pro-inflammatory cytokines in the ventral-midbrain revealed augmentation of TNF-α and IL-6 at middle age in both strains that reduced at old age, suggesting middle age as a critical, inflamm-aging-associated time point. TNF-α levels were high in C57BL/6 J, through aging and post-MPTP, while IL-6 and IL-1β were upregulated at old age. CD-1 had higher levels of anti-inflammatory cytokine TGF-β. MPTP challenge caused upregulation of enzymes MAO-A, MAO-B, and iNOS in both strains. Post-MPTP enhancement in fractalkine and hemeoxygenase-1 may be neuron-associated compensatory signals. Ultrastructural observations of elongated astroglial/microglial mitochondria vis-à-vis the shrunken ones in neurons suggest a scale-up of their functions with neurotoxic consequences. Thus, astroglia and microglia may modulate aging and PD susceptibility.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"13"},"PeriodicalIF":3.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000764","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: Sevoflurane Induces Learning and Memory Impairment in Young Mice Through a Reduction in Neuronal Glucose Transporter 3.","authors":"Jinpiao Zhu, Zongze Zhang, Junke Jia, Lirong Wang, Qiuyue Yang, Yanlin Wang, Chang Chen","doi":"10.1007/s10571-024-01520-2","DOIUrl":"https://doi.org/10.1007/s10571-024-01520-2","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"12"},"PeriodicalIF":3.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000768","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: Expression of CGRP in the Trigeminal Ganglion and Its Effect on the Polarization of Macrophages in Rats with Temporomandibular Arthritis.","authors":"Junli Tao, Xiaohui Wang, Jie Xu","doi":"10.1007/s10571-024-01527-9","DOIUrl":"10.1007/s10571-024-01527-9","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"11"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945430","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":"A Focal Traumatic Injury to the Neonatal Rodent Spinal Cord Causes an Immediate and Massive Spreading Depolarization Sustained by Chloride Ions, with Transient Network Dysfunction.","authors":"Atiyeh Mohammadshirazi, Graciela L Mazzone, Benjamín A Zylberberg, Giuliano Taccola","doi":"10.1007/s10571-024-01516-y","DOIUrl":"10.1007/s10571-024-01516-y","url":null,"abstract":"<p><p>In clinics, physical injuries to the spinal cord cause a temporary motor areflexia below lesion, known as spinal shock. This topic is still underexplored due to the lack of preclinical spinal cord injury (SCI) models that do not use anesthesia, which would affect spinal excitability. Our innovative design considered a custom-made micro impactor that provides localized and calibrated strikes to the ventral surface of the thoracic spinal cord of the entire CNS isolated from neonatal rats. Before and after injury, multiple ventral root (VR) recordings continuously traced respiratory rhythm, baseline spontaneous activities, and electrically induced reflex responses. As early as 200 ms after the lowering of the impactor, an immediate transient depolarization spread from the injury site to the whole spinal cord with distinct segmental velocities. Stronger strikes induced higher potentials causing, close by the site of injury, a transient drop in spinal cord oxygenation (SCO₂) and a massive cell death with a complete functional disconnection of input along the cord. Below the impact site, expiratory rhythm and spontaneous lumbar activity were suppressed. On lumbar VRs, reflex responses transiently halted but later recovered to control values, while electrically induced fictive locomotion remained perturbed. Moreover, low-ion modified Krebs solutions differently influenced impact-induced depolarizations, the magnitude of which amplified in low Cl^-. Overall, our novel ex vivo platform traces the immediate functional consequences of impacts to the spinal cord during development. This basic study provides insights on the SCI pathophysiology, unveiling an immediate chloride dysregulation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"10"},"PeriodicalIF":3.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913268","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":"Differences in Blood and Cerebrospinal Fluid Between Parkinson's Disease and Related Diseases.","authors":"Jie Ma, Zhijian Tang, Yaqi Wu, Jun Zhang, Zitao Wu, Lulu Huang, Shengwen Liu, Yu Wang","doi":"10.1007/s10571-024-01523-z","DOIUrl":"10.1007/s10571-024-01523-z","url":null,"abstract":"<p><p>It is difficult to distinguish Parkinson's disease (PD) in the early stage from those of various disorders including atypical Parkinson's syndrome (APS), vascular parkinsonism (VP), and even essential tremor (ET), because of the overlap of symptoms. Other, more challenging problems will arise when Parkinson's disease develops into Parkinson's disease dementia (PDD) in the middle and late stages. At this time, the differential diagnosis of PDD and DLB becomes thorny. These complicate the diagnostic process for PD, which traditionally heavily relies on symptomatic assessment and treatment response. Recent advances have identified several biomarkers in the blood and cerebrospinal fluid (CSF), including α-synuclein, lysosomal enzymes, fatty acid-binding proteins, and neurofilament light chain, whose concentration differs in PD and the related diseases. However, not all these molecules can effectively discriminate PD from related disorders. This review advocates for a paradigm shift toward biomarker-based diagnosis to effectively distinguish between PD and similar conditions. These biomarkers may reflect the diversity that exist among different diseases and provide an effective way to accurately understand their mechanisms. This review focused on blood and CSF biomarkers of PD that may have differential diagnostic value and the related molecular measurement methods with high diagnostic performance due to emerging technologies.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"9"},"PeriodicalIF":3.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892426","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 Signaling Pathways of Quercetin in Alzheimer's Disease: A Promising Arena.","authors":"Mansour A Alsaleem, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Mohammed Alrouji, Asmaa S A Yassen, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha","doi":"10.1007/s10571-024-01526-w","DOIUrl":"10.1007/s10571-024-01526-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and memory deficit. Even with extensive research and studies, presently, there is no effective treatment for the management of AD. Besides, most of drugs used in the treatment of AD did not avert the AD neuropathology, and the disease still in a progressive status. For example, acetyl cholinesterase inhibitors are associated with many adverse effects, such as insomnia and nightmares. As well, acetylcholinesterase inhibitors augment cholinergic neurotransmission leading to the development of adverse effects related to high acetylcholine level, such as salivation, rhinorrhea, vomiting, loss of appetite, and seizure. Furthermore, tacrine has poor bioavailability and causes hepatotoxicity. These commonly used drugs do not manage the original causes of AD. For those reasons, natural products were repurposed for the treatment of AD and neurodegenerative diseases. It has been shown that phytochemicals produce neuroprotective effects against the development and progression of neurodegenerative diseases by different mechanisms, including antioxidant and anti-inflammatory effects. Quercetin (QCN) has been reported to exert an effective neuroprotective effect against AD and other neurodegenerative diseases by lessening oxidative stress. In this review, electronic databases such as PubMed, Scopus, and Web of Science were searched for possible relevant studies and article linking the effect of QCN on AD. Findings from this review highlighted that many studies highlighted different mechanistic signaling pathways regarding the neuroprotective effect of QCN in AD. Nevertheless, the precise molecular mechanism of QCN in AD was not completely clarified. Consequently, this review aims to discuss the molecular mechanism of QCN in AD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"8"},"PeriodicalIF":3.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884975","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":"Glucocorticoid-Dependent Retinal Degeneration and Vision Impairment in Mice Susceptible to Prenatal Stress-Induced Behavioral Abnormalities.","authors":"Min-Ok Ryu, Ji-Youl Jung, Han Na Suh, Chung-Young Lee, Myung-Chul Kim, Ji Young Oh, Woo-Jin Song, Changhwan Ahn, Yeseul Yang, Gee Euhn Choi","doi":"10.1007/s10571-024-01525-x","DOIUrl":"10.1007/s10571-024-01525-x","url":null,"abstract":"<p><p>Chronic exposure to prenatal stress can impair neurogenesis and lead to irreversible cognitive and neuropsychiatric abnormalities in offspring. The retina is part of the nervous system; however, the impacts of prenatal stress on retinal neurogenesis and visual function remain unclear. This study examined how elevated prenatal glucocorticoid levels differentially affect retinal development in the offspring of pregnant mice exposed to chronic unpredictable mild stress (CUMS). Offspring were classified into control, stress-resilient, and stress-susceptible groups based on behavioral tests assessing spatial memory and depression-like behaviors. The stress-susceptible group exhibited significantly altered synaptogenesis, reduced ganglion cell development, decreased retinal thickness, and visiual impairment. These mice also showed a pervasive transformation of retinal astrocytes into a proinflammatory A1-like reactive state, evidenced by increased GFAP and decreased STAT3 expression levels. This astrocyte phenotype shift coincided with disruptions in neurogenesis and synaptic formation. Furthermore, prenatal exposure to exogenous corticosterone confirmed that the effects of prenatal stress are mediated by glucocorticoid-induced retinal neurodegeneration. Our findings suggest that elevated prenatal glucocorticoid levels trigger a series of neurodevelopmental disturbances leading to retinal neurodegeneration and vision impairment. This research highlights the impact of prenatal stress on retinal development and visual health, suggesting new avenues for understanding and potentially mitigating the negative effects of early-life stress on neurodevelopment.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"7"},"PeriodicalIF":3.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876286","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":"Application of Circulating Tumor DNA in the Auxiliary Diagnosis and Prognosis Prediction of Glioma.","authors":"Ying Lu, Zhouyu Wang, Danmeng Zhang, Ningning Luo, Hui Yang, Dongsheng Chen, Haixin Huang","doi":"10.1007/s10571-024-01515-z","DOIUrl":"10.1007/s10571-024-01515-z","url":null,"abstract":"<p><p>Glioma is the most common primary malignant brain tumor. Despite significant advances in the past decade in understanding the molecular pathogenesis of this tumor and exploring therapeutic strategies, the prognosis of patients with glioma remains poor. Accurate diagnosis of glioma is very important for the treatment and prognosis. Although the gold-standard method for the diagnosis and prognosis prediction of patients with glioma is tissue biopsy, it still has many limitations. Liquid biopsy can provide information on the auxiliary diagnosis and prognosis of gliomas. In this review, we summarized the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in the auxiliary diagnosis and prognosis of glioma. The common methods used to detect ctDNA in gliomas using samples including blood and cerebrospinal fluid (CSF) and the detection techniques for ctDNA, including droplet digital PCR (ddPCR) and next-generation sequencing (NGS), were discussed. Detection of ctDNA from plasma of patients with brain tumors remains challenging because of the blood-brain barrier (BBB). CSF has been proposed as a medium for ctDNA analysis in brain tumors, and mutation detection using plasma ctDNA was less sensitive than CSF ctDNA sequencing. Moreover, ongoing relevant clinical studies were summarized. Finally, we discussed the challenges, and future directions for the studies on ctDNA in glioma.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"6"},"PeriodicalIF":3.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846176","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":"Exploring the Neuroprotective Effects of Rufinamide in a Streptozotocin-Induced Dementia Model.","authors":"Darshpreet Kaur, Amarjot Kaur Grewal, Dalia Fouad, Amit Kumar, Varinder Singh, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha, Nermeen N Welson, Thakur Gurjeet Singh","doi":"10.1007/s10571-024-01521-1","DOIUrl":"10.1007/s10571-024-01521-1","url":null,"abstract":"<p><p>Due to the complex pathophysiology of AD (Alzheimer's Disease), there are currently no effective clinical treatments available, except for acetylcholinesterase inhibitors. However, CREB (cyclic AMP-responsive element binding protein) has been identified as the critical factor for the transcription in memory formation. Understanding the effect of potential drugs on the CREB pathway could lead to the development of new therapeutic molecules. Rufinamide has shown promise in improving memory in animal models, and these effects may be associated with modulation of the CREB pathway, however, this has not been previously reported. Thus, the present study aimed to determine the involvement of the CREB pathway in the cognitive improvement effects of rufinamide in STZ (streptozotocin) induced mouse model of dementia. Administration of STZ [3 mg/kg, i.c.v. (intracerebroventricular) bilaterally] significantly impaired cognitive performance in step-down passive avoidance and Morris water maze tests in animals, reduced brain endogenous antioxidant levels (GSH, superoxide dismutase, and catalase), and increased marker of brain oxidative stress [TBARS (thiobarbituric acid reactive substances)] and inflammation [IL-1β (Interleukin-1 beta), IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor alpha) and NF-κB (Nuclear factor kappa B)], along with neurodegeneration. These effects were markedly reversed by rufinamide (50 and 100 mg/kg) when administered to STZ animals. However, the pre-treatment with the CREB inhibitor (666-15) in STZ and rufinamide-administered animals neutralized the beneficial influence of rufinamide. Our data suggest that rufinamide, acting via CREB signaling, reduced oxidative stress and inflammatory markers while elevating anti-oxidant levels. Our study has established that rufinamide may act through CREB signaling in an investigational AD model, which could be crucial for developing new treatments beneficial in progressive neurological disorders.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"4"},"PeriodicalIF":3.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806257","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":"Single-Cell RNA-Seq Reveals the Pseudo-temporal Dynamic Evolution Characteristics of ADSCs to Neuronal Differentiation.","authors":"Xiaodong Yuan, Wen Li, Qing Liu, Ya Ou, Jing Li, Qi Yan, Pingshu Zhang","doi":"10.1007/s10571-024-01524-y","DOIUrl":"10.1007/s10571-024-01524-y","url":null,"abstract":"<p><p>Adipose-derived stromal cells (ADSCs) are commonly used in regenerative medicine, but the genetic features of their development into neuronal cells are unknown. This study used single-cell RNA sequencing (scRNA-seq) to reveal gene expression changes during ADSCs to neuronal differentiation. Sequencing of the ADSCs group, the prei-1d group, and the induction 1 h, 3 h, 5 h, 6 h, and 8 h groups was performed using the BD Rhapsody platform. Sequence data were analyzed using t-SNE, Monocle2, GO, and KEGG algorithms. Results showed that a total of 38,453 cells were collected, which were divided into 0-13 clusters. Monocle2 structured analysis revealed that ADSCs were located at the beginning of the trajectory, and the cells after 5 h of induction were mainly distributed at the end of the trajectory in branches 1 and 2. Up-regulated differentially expressed genes (DEGs) at 5 h after induction enriched GO items including cellular protein metabolism, cell adhesion, endocytosis, and cell migration. KEGG analysis showed that induced 6 h and 8 h groups mainly enriched pathways were oxidative phosphorylation, glutathione metabolism, and expression of Parkinson's disease-related genes. In conclusion, two distinct cell state mechanisms stimulate ADSCs to develop into mature neurons. ADSCs induced for 5 h had developed into mature neurons. Later, the differentiated cells undergo degenerative changes associated with senescence.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"5"},"PeriodicalIF":3.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805607","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}