Cellular and Molecular Neurobiology最新文献

{"title":"Correction to: The Neuroprotective Effects and Probable Mechanisms of Everolimus in a Rat Model of Intracerebral Hemorrhage","authors":"Shima Shirzad, F. Vafaee, F. Forouzanfar","doi":"10.1007/s10571-023-01441-6","DOIUrl":"https://doi.org/10.1007/s10571-023-01441-6","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"14 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138633031","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":"Association of mTOR Pathway and Conformational Alterations in C-Reactive Protein in Neurodegenerative Diseases and Infections.","authors":"Nitesh Kumar Poddar, Arshma Khan, Falak Fatima, Anshulika Saxena, Garima Ghaley, Shahanavaj Khan","doi":"10.1007/s10571-023-01402-z","DOIUrl":"10.1007/s10571-023-01402-z","url":null,"abstract":"<p><p>Inflammatory biomarkers have been very useful in detecting and monitoring inflammatory processes along with providing helpful information to select appropriate therapeutic strategies. C-reactive protein (CRP) is a nonspecific, but quite useful medical acute inflammatory biomarker and is associated with persistent chronic inflammatory processes. Several studies suggest that different levels of CRP are correlated with neurological disorders such as Alzheimer's disease (AD). However, dynamics of CRP levels have also been observed in virus/bacterial-related infections leading to inflammatory responses and this triggers mTOR-mediated pathways for neurodegeneration diseases. The biophysical structural transition from CRP to monomeric CRP (mCRP) and the significance of the ratio of CRP levels on the onset of symptoms associated with inflammatory response have been discussed. In addition, mTOR inhibitors act as immunomodulators by downregulating the expression of viral infection and can be explored as a potential therapy for neurological diseases.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"3815-3832"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10149948","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":"Activation of TRPV1 Channels Inhibits the Release of Acetylcholine and Improves Muscle Contractility in Mice.","authors":"Arsenii Y Arkhipov, Nikita S Fedorov, Leniz F Nurullin, Aydar N Khabibrakhmanov, Marat A Mukhamedyarov, Dmitry V Samigullin, Artem I Malomouzh","doi":"10.1007/s10571-023-01403-y","DOIUrl":"10.1007/s10571-023-01403-y","url":null,"abstract":"<p><p>TRPV1 represents a non-selective transient receptor potential cation channel found not only in sensory neurons, but also in motor nerve endings and in skeletal muscle fibers. However, the role of TRPV1 in the functioning of the neuromuscular junction has not yet been fully established. In this study, the Levator Auris Longus muscle preparations were used to assess the effect of pharmacological activation of TRPV1 channels on neuromuscular transmission. The presence of TRPV1 channels in the nerve terminal and in the muscle fiber was confirmed by immunohistochemistry. It was verified by electrophysiology that the TRPV1 channel agonist capsaicin inhibits the acetylcholine release, and this effect was completely absent after preliminary application of the TRPV1 channel blocker SB 366791. Nerve stimulation revealed an increase of amplitude of isometric tetanic contractions upon application of capsaicin which was also eliminated after preliminary application of SB 366791. Similar data were obtained during direct muscle stimulation. Thus, pharmacological activation of TRPV1 channels affects the functioning of both the pre- and postsynaptic compartment of the neuromuscular junction. A moderate decrease in the amount of acetylcholine released from the motor nerve allows to maintain a reserve pool of the mediator to ensure a longer signal transmission process, and an increase in the force of muscle contraction, in its turn, also implies more effective physiological muscle activity in response to prolonged stimulation. This assumption is supported by the fact that when muscle was indirect stimulated with a fatigue protocol, muscle fatigue was attenuated in the presence of capsaicin.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4157-4172"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193524","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":"Heterozygous FOXJ1 Mutations Cause Incomplete Ependymal Cell Differentiation and Communicating Hydrocephalus.","authors":"Connie C Hou, Danielle Li, Bethany C Berry, Shaokuan Zheng, Rona S Carroll, Mark D Johnson, Hong Wei Yang","doi":"10.1007/s10571-023-01398-6","DOIUrl":"10.1007/s10571-023-01398-6","url":null,"abstract":"<p><p>Heterozygous mutations affecting FOXJ1, a transcription factor governing multiciliated cell development, have been associated with obstructive hydrocephalus in humans. However, factors that disrupt multiciliated ependymal cell function often cause communicating hydrocephalus, raising questions about whether FOXJ1 mutations cause hydrocephalus primarily by blocking cerebrospinal fluid (CSF) flow or by different mechanisms. Here, we show that heterozygous FOXJ1 mutations are also associated with communicating hydrocephalus in humans and cause communicating hydrocephalus in mice. Disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation and communicating hydrocephalus. Mature ependymal cell number and motile cilia number are decreased, and 12% of motile cilia display abnormal axonemes. We observed decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and a disruption of unidirectional CSF flow. Thus, heterozygous FOXJ1 mutations impair ventricular multiciliated cell differentiation, thereby causing communicating hydrocephalus. CSF flow obstruction may develop secondarily in some patients harboring FOXJ1 mutations. Heterozygous FOXJ1 mutations impair motile cilia structure and basal body alignment, thereby disrupting CSF flow dynamics and causing communicating hydrocephalus.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4103-4116"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067688","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 Neuroprotective Effects and Probable Mechanisms of Everolimus in a Rat Model of Intracerebral Hemorrhage.","authors":"Shima Shirzad, Farzaneh Vafaee, Fatemeh Forouzanfar","doi":"10.1007/s10571-023-01409-6","DOIUrl":"10.1007/s10571-023-01409-6","url":null,"abstract":"<p><p>Mammalian target of rapamycin (mTOR) is a central regulator of cellular growth and homeostasis. Changes in mTOR activity are often observed in many neurological diseases, such as stroke. Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity. However, there are currently no treatments that have been shown to enhance outcomes following ICH, so new treatments are urgently required. In this study, a selective mTOR inhibitor, everolimus, was applied to investigate the outcome after ICH and the possible underlying mechanism. The ICH model was established by autologous blood injection. Everolimus (50 and 100 µg/kg) was administered intraperitoneally for 14 consecutive days' post-operation. The neurological functions were examined at 3, 7, and 14 days' post-ICH. Samples of brain tissue were collected to perform histopathological and immunohistochemical (NF-k-positive cell) examinations. Besides, the striatum was used to evaluate parameters related to oxidative stress (superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels) and inflammation markers (TNF-α and NO). Everolimus ameliorated ICH-induced neurological deficits. In addition, treatment with everolimus reduced infarct volume and NF-k-β positive cells as compared to the ICH group. Furthermore, everolimus significantly increased total thiol content and SOD activity while significantly reducing MDA, NO, and TNF- levels as compared to the ICH group. Collectively, our investigation showed that everolimus improves ICH outcome and modulates oxidative stress and inflammation after ICH. Treatment with rapamycin reduced neurological deficient, oxidative stress, and inflammation in a rat model of intracerebral hemorrhage.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4219-4230"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108676","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":"Effects of Ischemic Stroke on Interstitial Fluid Clearance in Mouse Brain: a Bead Study.","authors":"Tuo Yang, Yang Sun, Qianqian Li, Nour Alraqmany, Feng Zhang","doi":"10.1007/s10571-023-01400-1","DOIUrl":"10.1007/s10571-023-01400-1","url":null,"abstract":"<p><p>The clearance of brain interstitial fluid (ISF) is important in maintaining brain homeostasis. ISF clearance impairment leads to toxic material accumulation in the brain, and ischemic stroke could impair ISF clearance. The present study investigates ISF clearance under normal and ischemic conditions. The carboxylate-modified FluoSpheres beads (0.04 μm in diameter) were injected into the striatum. Sham or transient middle cerebral artery occlusion surgeries were performed on the mice. The brain sections were immunostained with cell markers, and bead distribution at various time points was examined with a confocal microscope. Primary mouse neuronal cultures were incubated with the beads to explore in vitro endocytosis.  Two physiological routes for ISF clearance were identified. The main one was to the lateral ventricle (LV) through the cleft between the striatum and the corpus callosum (CC)/external capsule (EC), where some beads were captured by the ependymal macrophages and choroid plexus. An alternative and minor route was to the subarachnoid space through the CC/EC and the cortex, where some of the beads were endocytosed by neurons. After ischemic stroke, a significant decrease in the main route and an increase in the minor route were observed. Additionally, microglia/macrophages engulfed the beads in the infarction. In conclusion, we report that the physiological clearance of ISF and beads mainly passes through the cleft between the CC/EC and striatum into the LV, or alternatively through the cortex into the subarachnoid space. Stroke delays the main route but enhances the minor route, and microglia/macrophages engulf the beads in the infarction. Ischemic stroke impairs the clearance of brain interstitial fluid/beads. Under physiological conditions, the main route ( ① ) of interstitial fluid clearance is to the lateral ventricle, and the minor one ( ② ) is to the subarachnoid space. Ischemic stroke weakens the main route ( ① ), enhances the minor one ( ② ), and leads to microglial/macrophage phagocytosis within the infarction ( ③ ).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4141-4156"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074456","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":"High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin.","authors":"Kayvan Khoramipour, Maryam Hossein Rezaei, Elham Madadizadeh, Mahdieh Sadat Hosseini, Zahra Soltani, Janis Schierbauer, Othmar Moser","doi":"10.1007/s10571-023-01421-w","DOIUrl":"10.1007/s10571-023-01421-w","url":null,"abstract":"<p><p>Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4295-4307"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41192690","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":"The Role of Oxidative Stress in Trisomy 21 Phenotype.","authors":"Angelika Buczyńska, Iwona Sidorkiewicz, Adam Jacek Krętowski, Monika Zbucka-Krętowska","doi":"10.1007/s10571-023-01417-6","DOIUrl":"10.1007/s10571-023-01417-6","url":null,"abstract":"<p><p>Extensive research has been conducted to gain a deeper understanding of the deregulated metabolic pathways in the development of trisomy 21 (T21) or Down syndrome. This research has shed light on the hypothesis that oxidative stress plays a significant role in the manifestation of the T21 phenotype. Although in vivo studies have shown promising results in mitigating the detrimental effects of oxidative stress, there is currently a lack of introduced antioxidant treatment options targeting cognitive impairments associated with T21. To address this gap, a comprehensive literature review was conducted to provide an updated overview of the involvement of oxidative stress in T21. The review aimed to summarize the insights into the pathogenesis of the Down syndrome phenotype and present the findings of recent innovative research that focuses on improving cognitive function in T21 through various antioxidant interventions. By examining the existing literature, this research seeks to provide a holistic understanding of the role oxidative stress plays in the development of T21 and to explore novel approaches that target multiple aspects of antioxidant intervention to improve cognitive function in individuals with Down syndrome. The guides -base systematic review process (Hutton et al. 2015).</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"3943-3963"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41192692","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":"Antioxidant System and Endoplasmic Reticulum Stress in Cataracts.","authors":"Xi Zhang, Bingqing Liu, Kevin Lal, Haihua Liu, Myhoa Tran, Manyu Zhou, Chimdindu Ezugwu, Xin Gao, Terry Dang, My-Lien Au, Erica Brown, Hongli Wu, Yan Liao","doi":"10.1007/s10571-023-01427-4","DOIUrl":"10.1007/s10571-023-01427-4","url":null,"abstract":"<p><p>The primary underlying contributor for cataract, a leading cause of vision impairment and blindness worldwide, is oxidative stress. Oxidative stress triggers protein damage, cell apoptosis, and subsequent cataract formation. The nuclear factor-erythroid 2-related factor 2 (Nrf2) serves as a principal redox transcriptional factor in the lens, offering a line of defense against oxidative stress. In response to oxidative challenges, Nrf2 dissociates from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1), moves to the nucleus, and binds to the antioxidant response element (ARE) to activate the Nrf2-dependent antioxidant system. In parallel, oxidative stress also induces endoplasmic reticulum stress (ERS). Reactive oxygen species (ROS), generated during oxidative stress, can directly damage proteins, causing them to misfold. Initially, the unfolded protein response (UPR) activates to mitigate excessive misfolded proteins. Yet, under persistent or severe stress, the failure to rectify protein misfolding leads to an accumulation of these aberrant proteins, pushing the UPR towards an apoptotic pathway, further contributing to cataractogenesis. Importantly, there is a dynamic interaction between the Nrf2 antioxidant system and the ERS/UPR mechanism in the lens. This interplay, where ERS/UPR can modulate Nrf2 expression and vice versa, holds potential therapeutic implications for cataract prevention and treatment. This review explores the intricate crosstalk between these systems, aiming to illuminate strategies for future advancements in cataract prevention and intervention. The Nrf2-dependent antioxidant system communicates and cross-talks with the ERS/UPR pathway. Both mechanisms are proposed to play pivotal roles in the onset of cataract formation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4041-4058"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688897","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":"BDNF and Lactate as Modulators of Hippocampal CA3 Network Physiology.","authors":"Ernesto Griego, Emilio J Galván","doi":"10.1007/s10571-023-01425-6","DOIUrl":"10.1007/s10571-023-01425-6","url":null,"abstract":"<p><p>Growing evidence supports the notion that brain-derived neurotrophic factor (BDNF) and lactate are potent modulators of mammalian brain function. The modulatory actions of those biomolecules influence a wide range of neuronal responses, from the shaping of neuronal excitability to the induction and expression of structural and synaptic plasticity. The biological actions of BDNF and lactate are mediated by their cognate receptors and specific transporters located in the neuronal membrane. Canonical functions of BDNF occur via the tropomyosin-related kinase B receptor (TrkB), whereas lactate acts via monocarboxylate transporters or the hydroxycarboxylic acid receptor 1 (HCAR1). Both receptors are highly expressed in the central nervous system, and some of their physiological actions are particularly well characterized in the hippocampus, a brain structure involved in the neurophysiology of learning and memory. The multifarious neuronal circuitry between the axons of the dentate gyrus granule cells, mossy fibers (MF), and pyramidal neurons of area CA3 is of great interest given its role in specific mnemonic processes and involvement in a growing number of brain disorders. Whereas the modulation exerted by BDNF via TrkB has been extensively studied, the influence of lactate via HCAR1 on the properties of the MF-CA3 circuit is an emerging field. In this review, we discuss the role of both systems in the modulation of brain physiology, with emphasis on the hippocampal CA3 network. We complement this review with original data that suggest cross-modulation is exerted by these two independent neuromodulatory systems.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":"4007-4022"},"PeriodicalIF":4.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688898","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}