ASN NEURO最新文献

{"title":"The Initial Myelination in the Central Nervous System.","authors":"Qiang Yu,&nbsp;Teng Guan,&nbsp;Ying Guo,&nbsp;Jiming Kong","doi":"10.1177/17590914231163039","DOIUrl":"https://doi.org/10.1177/17590914231163039","url":null,"abstract":"<p><p>Myelination contributes not only to the rapid nerve conduction but also to axonal insulation and protection. In the central nervous system (CNS), the initial myelination features a multistep process where oligodendrocyte precursor cells undergo proliferation and migration before differentiating into mature oligodendrocytes. Mature oligodendrocytes then extend processes and wrap around axons to form the multilayered myelin sheath. These steps are tightly regulated by various cellular and molecular mechanisms, such as transcription factors (Olig family, Sox family), growth factors (PDGF, BDNF, FGF-2, IGF), chemokines/cytokines (TGF-β, IL-1β, TNFα, IL-6, IFN-γ), hormones (T3), axonal signals (PSA-NCAM, L1-CAM, LINGO-1, neural activity), and intracellular signaling pathways (Wnt/β-catenin, PI3 K/AKT/mTOR, ERK/MAPK). However, the fundamental mechanisms for initial myelination are yet to be fully elucidated. Identifying pivotal mechanisms for myelination onset, development, and repair will become the focus of future studies. This review focuses on the current understanding of how CNS myelination is initiated and also the regulatory mechanisms underlying the process.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231163039"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/0c/10.1177_17590914231163039.PMC10052612.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9884819","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":"Regulation of the Volume-Regulated Anion Channel Pore-Forming Subunit LRRC8A in the Intrahippocampal Kainic Acid Model of Mesial Temporal Lobe Epilepsy.","authors":"Manolia R Ghouli, Carrie R Jonak, Rajan Sah, Todd A Fiacco, Devin K Binder","doi":"10.1177/17590914231184072","DOIUrl":"10.1177/17590914231184072","url":null,"abstract":"<p><p>Volume-regulated anion channels (VRACs) are a group of ubiquitously expressed outwardly-rectifying anion channels that sense increases in cell volume and act to return cells to baseline volume through an efflux of anions and organic osmolytes, including glutamate. Because cell swelling, increased extracellular glutamate levels, and reduction of the brain extracellular space (ECS) all occur during seizure generation, we set out to determine whether VRACs are dysregulated throughout mesial temporal lobe epilepsy (MTLE), the most common form of adult epilepsy. To accomplish this, we employed the IHKA experimental model of MTLE, and probed for the expression of LRRC8A, the essential pore-forming VRAC subunit, at acute, early-, mid-, and late-epileptogenic time points (1-, 7-, 14-, and 30-days post-IHKA, respectively). Western blot analysis revealed the upregulation of total dorsal hippocampal LRRC8A 14-days post-IHKA in both the ipsilateral and contralateral hippocampus. Immunohistochemical analyses showed an increased LRRC8A signal 7-days post-IHKA in both the ipsilateral and contralateral hippocampus, along with layer-specific changes 1-, 7-, and 30-days post-IHKA bilaterally. LRRC8A upregulation 1 day post-IHKA was observed primarily in astrocytes; however, some upregulation was also observed in neurons. Glutamate-GABA/glutamine cycle enzymes glutamic acid decarboxylase, glutaminase, and glutamine synthetase were also dysregulated at the 7-day timepoint post status epilepticus. The timepoint-dependent upregulation of total hippocampal LRRC8A and the possible subsequent increased efflux of glutamate in the epileptic hippocampus suggest that the dysregulation of astrocytic VRAC may play an important role in the development of epilepsy.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231184072"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/15/10.1177_17590914231184072.PMC10331354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181528","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":"All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration.","authors":"Gonzalo Piñero, Marianela Vence, Marcos L Aranda, Magalí C Cercato, Paula A Soto, Vanina Usach, Patricia C Setton-Avruj","doi":"10.1177/17590914231167281","DOIUrl":"10.1177/17590914231167281","url":null,"abstract":"<p><strong>Summary statement: </strong>Bone marrow cell transplant has proven to be an effective therapeutic approach to treat peripheral nervous system injuries as it not only promoted regeneration and remyelination of the injured nerve but also had a potent effect on neuropathic pain.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231167281"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/c2/10.1177_17590914231167281.PMC10475269.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10523566","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":"Müller Glia to Müller Glia Extracellular Vesicle-Dependent Signaling Induces Multipotency Genes <i>Nestin</i> and l<i>in28</i> Expression in Response to N-methyl-D-aspartate (NMDA) Exposure.","authors":"Ana Karen Carapia,&nbsp;Erick J Martinez-Colin,&nbsp;Deisy Segura-Villalobos,&nbsp;Rebeca Yael Victoria-Chavez,&nbsp;Ivonne Lezama,&nbsp;Eduardo Martinez-Martinez,&nbsp;Monica Lamas","doi":"10.1177/17590914231183272","DOIUrl":"https://doi.org/10.1177/17590914231183272","url":null,"abstract":"<p><strong>Summary statement: </strong>Retinal Müller cells secrete extracellular vesicles that can be captured by other Müller cells. In response to a signal that may be deleterious for the retina, Müller glia-derived extracellular vesicles spread instructions to induce gene expression changes in other cells.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231183272"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/f4/10.1177_17590914231183272.PMC10291543.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710241","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 α₂ Adrenoceptor Agonist and Sedative/Anaesthetic Dexmedetomidine Excites Diverse Neuronal Types in the Ventrolateral Preoptic Area of Male Mice.","authors":"Sumei Fan, Xinqi Cheng, Pingping Zhang, Yuanyin Wang, Liecheng Wang, Juan Cheng","doi":"10.1177/17590914231191016","DOIUrl":"10.1177/17590914231191016","url":null,"abstract":"<p><strong>Summary statement: </strong>Dexmedetomidine is an important ICU sedative. The mechanism of dexmedetomidine is not fully understood. Activating NA(-) and NA(+) neurons in the VLPO by dexmedetomidine using polysomnography and electrophysiological recording, this may explain the unique sedative properties with rapid arousal.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231191016"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/49/10.1177_17590914231191016.PMC10388635.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9909794","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":"Activation of the PACAP/PAC1 Signaling Pathway Accelerates the Repair of Impaired Spatial Memory Caused by an Ultradian Light Cycle.","authors":"Dejiao Xu,&nbsp;Ying Zhang,&nbsp;Jun Feng,&nbsp;Hongyu Fu,&nbsp;Jiayi Li,&nbsp;Wei Wang,&nbsp;Zhen Li,&nbsp;Pingping Zhang,&nbsp;Xinqi Cheng,&nbsp;Liecheng Wang,&nbsp;Juan Cheng","doi":"10.1177/17590914231169140","DOIUrl":"https://doi.org/10.1177/17590914231169140","url":null,"abstract":"<p><p>The mechanism of light-induced spatial memory deficits, as well as whether rhythmic expression of the pituitary adenylyl cyclase-activating polypeptides (PACAP)-PAC1 pathway influenced by light is related to this process, remains unclear. Here, we aimed to investigate the role of the PACAP-PAC1 pathway in light-mediated spatial memory deficits. Animals were first housed under a T24 cycle (12 h light:12 h dark), and then light conditions were transformed to a T7 cycle (3.5 h light:3.5 h dark) for at least 4 weeks. The spatial memory function was assessed using the Morris water maze (MWM). In line with behavioral studies, rhythmic expression of the PAC1 receptor and glutamate receptors in the hippocampal CA1 region was assessed by western blotting, and electrophysiology experiments were performed to determine the influence of the PACAP-PAC1 pathway on neuronal excitability and synaptic signaling transmission. Spatial memory was deficient after mice were exposed to the T7 light cycle. Rhythmic expression of the PAC1 receptor was dramatically decreased, and the excitability of CA1 pyramidal cells was decreased in T7 cycle-housed mice. Compensation with PACAP1-38, a PAC1 receptor agonist, helped T7 cycle-housed mouse CA1 pyramidal cells recover neuronal excitability to normal levels, and cannulas injected with PACAP1-38 shortened the time to find the platform in MWM. Importantly, the T7 cycle decreased the frequency of AMPA receptor-mediated excitatory postsynaptic currents. In conclusion, the PACAP-PAC1 pathway is an important protective factor modulating light-induced spatial memory function deficits, affecting CA1 pyramidal cell excitability and excitatory synaptic signaling transmission.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231169140"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/b4/10.1177_17590914231169140.PMC10123913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507389","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":"Hippocampus Insulin Receptors Regulate Episodic and Spatial Memory Through Excitatory/Inhibitory Balance.","authors":"Cai-Yan Xue, Tian Gao, E Mao, Zhen-Zhen Kou, Ling Dong, Feng Gao","doi":"10.1177/17590914231206657","DOIUrl":"10.1177/17590914231206657","url":null,"abstract":"<p><p>It is well known that the hippocampus is a vital brain region playing a key role in both episodic and spatial memory. Insulin receptors (InsRs) are densely distributed in the hippocampus and are important for its function. However, the effects of InsRs on the function of the specific hippocampal cell types remain elusive. In this study, hippocampal InsRs knockout mice had impaired episodic and spatial memory. GABAergic neurons and glutamatergic neurons in the hippocampus are involved in the balance between excitatory and inhibitory (E/I) states and participate in the processes of episodic and spatial memory. InsRs are located mainly at excitatory neurons in the hippocampus, whereas 8.5% of InsRs are glutamic acid decarboxylase 2 (GAD2)::Ai9-positive (GABAergic) neurons. Next, we constructed a transgenic mouse system in which InsR expression was deleted from GABAergic (glutamate decarboxylase 2::InsR^fl/fl, GAD2^Cre::InsR^fl/fl) or glutamatergic neurons (vesicular glutamate transporter 2::InsR^fl/fl,Vglut2^Cre::InsR^fl/fl). Our results showed that in comparison to the InsR^fl/fl mice, both episodic and spatial memory were lower in GAD2^Cre::InsR^fl/fl and Vglut2^Cre::InsR^fl/fl. In addition, both GAD2^Cre::InsR^fl/fl and Vglut2^Cre::InsR^fl/fl were associated with more anxiety and lower glucose tolerance. These findings reveal that hippocampal InsRs might be crucial for episodic and spatial memory through E/I balance hippocampal regulation.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231206657"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420255","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":"Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice.","authors":"Fei Zeng, Karsten Parker, Yanqiang Zhan, Matthew Miller, Meng-Yang Zhu","doi":"10.1177/17590914231152099","DOIUrl":"10.1177/17590914231152099","url":null,"abstract":"<p><strong>Summary statement: </strong>The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231152099"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/ad/10.1177_17590914231152099.PMC9880594.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10784089","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":"Advancements in a FRET Biosensor for Live-Cell Fluorescence-Lifetime High-Throughput Screening of Alpha-Synuclein.","authors":"Anthony R Braun, Noah Nathan Kochen, Samantha L Yuen, Elly E Liao, Razvan L Cornea, David D Thomas, Jonathan N Sachs","doi":"10.1177/17590914231184086","DOIUrl":"10.1177/17590914231184086","url":null,"abstract":"<p><p>There is a critical need for small molecules capable of rescuing pathophysiological phenotypes induced by alpha-synuclein (aSyn) misfolding and oligomerization. Building upon our previous aSyn cellular fluorescence lifetime (FLT)-Förster resonance energy transfer (FRET) biosensors, we have developed an inducible cell model incorporating the red-shifted mCyRFP1/mMaroon1 (OFP/MFP) FRET pair. This new aSyn FRET biosensor improves the signal-to-noise ratio, reduces nonspecific background FRET, and results in a 4-fold increase (transient transfection) and 2-fold increase (stable, inducible cell lines) in FRET signal relative to our previous GFP/RFP aSyn biosensors. The inducible system institutes greater temporal control and scalability, allowing for fine-tuning of biosensor expression and minimizes cellular cytotoxicity due to overexpression of aSyn. Using these inducible aSyn-OFP/MFP biosensors, we screened the Selleck library of 2684 commercially available, FDA-approved compounds and identified proanthocyanidins and casanthranol as novel hits. Secondary assays validated the ability of these compounds to modulate aSyn FLT-FRET. Functional assays probing cellular cytotoxicity and aSyn fibrillization demonstrated their capability to inhibit seeded aSyn fibrillization. Proanthocyanidins completely rescued aSyn fibril-induced cellular toxicity with EC₅₀ of 200 nM and casanthranol supported a 85.5% rescue with a projected EC₅₀ of 34.2 μM. Furthermore, proanthocyanidins provide a valuable tool compound to validate our aSyn biosensor performance in future high-throughput screening campaigns of industrial-scale (million-compound) chemical libraries.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231184086"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/09/10.1177_17590914231184086.PMC10338669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169777","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":"Diazepam Binding Inhibitor Control of Eu- and Hypoglycemic Patterns of Ventromedial Hypothalamic Nucleus Glucose-Regulatory Signaling.","authors":"Sagor C Roy, Subash Sapkota, Madhu Babu Pasula, Khaggeswar Bheemanapally, Karen P Briski","doi":"10.1177/17590914231214116","DOIUrl":"10.1177/17590914231214116","url":null,"abstract":"<p><p>Pharmacological stimulation/antagonism of astrocyte glio-peptide octadecaneuropeptide signaling alters ventromedial hypothalamic nucleus (VMN) counterregulatory γ-aminobutyric acid (GABA) and nitric oxide transmission. The current research used newly developed capillary zone electrophoresis-mass spectrometry methods to investigate hypoglycemia effects on VMN octadecaneuropeptide content, along with gene knockdown tools to determine if octadecaneuropeptide signaling regulates these transmitters during eu- and/or hypoglycemia. Hypoglycemia caused dissimilar adjustments in the octadecaneuropeptide precursor, i.e., diazepam-binding-inhibitor and octadecaneuropeptide levels in dorsomedial versus ventrolateral VMN. Intra-VMN diazepam-binding-inhibitor siRNA administration decreased baseline 67 and 65 kDa glutamate decarboxylase mRNA levels in GABAergic neurons laser-microdissected from each location, but only affected hypoglycemic transcript expression in ventrolateral VMN. This knockdown therapy imposed dissimilar effects on eu- and hypoglycemic glucokinase and 5'-AMP-activated protein kinase-alpha1 (AMPKα1) and -alpha2 (AMPKα2) gene profiles in dorsomedial versus ventrolateral GABAergic neurons. Diazepam-binding-inhibitor gene silencing up-regulated baseline (dorsomedial) or hypoglycemic (ventrolateral) nitrergic neuron neuronal nitric oxide synthase mRNA profiles. Baseline nitrergic cell glucokinase mRNA was up- (ventrolateral) or down- (dorsomedial) regulated by diazepam-binding-inhibitor siRNA, but knockdown enhanced hypoglycemic profiles in both sites. Nitrergic nerve cell AMPKα1 and -α2 transcripts exhibited division-specific responses to this genetic manipulation during eu- and hypoglycemia. Results document the utility of capillary zone electrophoresis-mass spectrometric tools for quantification of ODN in small-volume brain tissue samples. Data show that hypoglycemia has dissimilar effects on ODN signaling in the two major neuroanatomical divisions of the VMN and that this glio-peptide imposes differential control of glucose-regulatory neurotransmission in the VMNdm versus VMNvl during eu- and hypoglycemia.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"15 ","pages":"17590914231214116"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457577","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}