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1.
Sud Med Ekspert ; 63(1): 53-55, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32040089

RESUMO

Aim of this study is to establish a possibility of finding morphologic signs of diffuse axonal injury early after the injury. Use of immunohistochemical examination of the brain to detect protein ß-APP made it possible not only to diagnose this condition correctly, but also to reasonably and categorically answer the question of a causal relationship between causing damage and the onset of death.


Assuntos
Lesões Encefálicas , Lesão Axonal Difusa , Precursor de Proteína beta-Amiloide , Axônios , Encéfalo/patologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/patologia , Causas de Morte , Lesão Axonal Difusa/diagnóstico , Lesão Axonal Difusa/patologia , Humanos , Imuno-Histoquímica
2.
Chin J Physiol ; 63(1): 1-6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32056980

RESUMO

The purpose of this study was to quantitatively assess the difference in sudomotor function between healthy males and females in their early twenties by measuring skin surface area and activated sweat gland density (ASGD). The quantitative sudomotor axon reflex test (QSART), a method for evaluating autonomic nervous system activity, was used for quantification. In QSART, the sweat glands are activated directly or indirectly by the subcutaneous application of neurotransmitters, such as acetylcholine, through iontophoresis. This series of mechanisms is called the sudomotor axon reflex. After recording age, height, weight, and several measurements of the forearm, QSART was performed on 101 healthy controls aged 21-26 years to measure ASGD. The mean temperature and humidity on the measurement days were 11.4°C and 58.1% on May 3, 2018, and 14.7°C and 70.3% on May 10, 2018. The result of independent sample t-test showed higher ASGD in women (P < 0.05). The body surface area and the surface area of the forearms were higher in men (P < 0.001), but the number of activated sweat glands was not significantly different according to sex. The activated sweat gland counts of the body and forearms were analyzed through linear regression by age for males and females. Except for the activated sweat gland count of the male body, the analysis showed a tendency to decrease with increasing age but was not statistically significant in any case (P > 0.05). Showing insufficient coefficient of determination (R2), multiple regression analyses with sex and ages did not correct this insignificance between age and activated sweat gland count.


Assuntos
Glândulas Sudoríparas , Sudorese , Adulto , Axônios , Feminino , Humanos , Iontoforese , Masculino , Reflexo , Adulto Jovem
3.
Nat Commun ; 11(1): 100, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900387

RESUMO

Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons.


Assuntos
Segmento Inicial do Axônio/metabolismo , Proteoma/metabolismo , Animais , Axônios , Biotinilação , Humanos , Espectrometria de Massas , Camundongos , Neurônios/metabolismo , Transporte Proteico , Ratos , Ratos Sprague-Dawley
4.
Nat Commun ; 11(1): 133, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919407

RESUMO

Neurons are subjected to strain due to body movement and their location within organs and tissues. However, how they withstand these forces over the lifetime of an organism is still poorly understood. Here, focusing on touch receptor neuron-epidermis interactions using Caenorhabditis elegans as a model system, we show that UNC-70/ß-spectrin and TBC-10, a conserved GTPase-activating protein, function non-cell-autonomously within the epidermis to dynamically maintain attachment of the axon. We reveal that, in response to strain, UNC-70/ß-spectrin and TBC-10 stabilize trans-epidermal hemidesmosome attachment structures which otherwise become lost, causing axonal breakage and degeneration. Furthermore, we show that TBC-10 regulates axonal attachment and maintenance by inactivating RAB-35, and reveal functional conservation of these molecules with their vertebrate orthologs. Finally, we demonstrate that ß-spectrin functions in this context non-cell-autonomously. We propose a model in which mechanically resistant epidermal attachment structures are maintained by UNC-70/ß-spectrin and TBC-10 during movement, preventing axonal detachment and degeneration.


Assuntos
Axônios/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , Espectrina/metabolismo , Estresse Fisiológico/fisiologia , Animais , Citoesqueleto/fisiologia , Epiderme/metabolismo , Hemidesmossomos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
5.
Neuron ; 105(2): 207-209, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31972142

RESUMO

In this issue of Neuron, Yang et al. (2020) identify glycerolipid metabolism as a neuron-intrinsic mechanism that regulates axonal growth and regeneration. Shifting glycerolipid metabolism toward increased triglyceride synthesis blocks PNS neuron regeneration, whereas shifting it toward membrane phospholipid synthesis overcomes regeneration failure in CNS neurons.


Assuntos
Axônios , Regeneração Nervosa , Neurônios
6.
Neuron ; 105(2): 209-211, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31972143

RESUMO

Axonal projection patterns are increasingly recognized as a defining feature for neuronal classification. How could such structural distinctions be linked to functions? In this issue of Neuron, Tang and Higley (2020) disambiguate behavior-level functions of two projection-defined subtypes of cortical projection neurons.


Assuntos
Neurônios , Células Piramidais , Axônios , Interneurônios
7.
Nat Rev Neurol ; 16(2): 69-83, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959938

RESUMO

Essential tremor (ET) is the most common tremor disorder globally and is characterized by kinetic tremor of the upper limbs, although other clinical features can also occur. Postmortem studies are a particularly important avenue for advancing our understanding of the pathogenesis of ET; however, until recently, the number of such studies has been limited. Several recent postmortem studies have made important contributions to our understanding of the pathological changes that take place in ET. These studies identified abnormalities in the cerebellum, which primarily affected Purkinje cells (PCs), basket cells and climbing fibres, in individuals with ET. We suggest that some of these pathological changes (for example, focal PC axonal swellings, swellings in and regression of the PC dendritic arbor and PC death) are likely to be primary and degenerative. By contrast, other changes, such as an increase in PC recurrent axonal collateral formation and hypertrophy of GABAergic basket cell axonal processes, could be compensatory responses to restore cerebellar GABAergic tone and cerebellar cortical inhibitory efficacy. Such compensatory responses are likely to be insufficient, enabling the disease to progress. Here, we review the results of recent postmortem studies of ET and attempt to place these findings into an anatomical-physiological disease model.


Assuntos
Tremor Essencial/patologia , Vias Neurais/patologia , Doenças Neurodegenerativas/patologia , Axônios/patologia , Humanos , Fibras Nervosas/patologia , Neurônios/patologia
8.
Genes Dev ; 34(3-4): 194-208, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31919191

RESUMO

Promoting axon regeneration in the central and peripheral nervous system is of clinical importance in neural injury and neurodegenerative diseases. Both pro- and antiregeneration factors are being identified. We previously reported that the Rtca mediated RNA repair/splicing pathway restricts axon regeneration by inhibiting the nonconventional splicing of Xbp1 mRNA under cellular stress. However, the downstream effectors remain unknown. Here, through transcriptome profiling, we show that the tubulin polymerization-promoting protein (TPPP) ringmaker/ringer is dramatically increased in Rtca-deficient Drosophila sensory neurons, which is dependent on Xbp1. Ringer is expressed in sensory neurons before and after injury, and is cell-autonomously required for axon regeneration. While loss of ringer abolishes the regeneration enhancement in Rtca mutants, its overexpression is sufficient to promote regeneration both in the peripheral and central nervous system. Ringer maintains microtubule stability/dynamics with the microtubule-associated protein futsch/MAP1B, which is also required for axon regeneration. Furthermore, ringer lies downstream from and is negatively regulated by the microtubule-associated deacetylase HDAC6, which functions as a regeneration inhibitor. Taken together, our findings suggest that ringer acts as a hub for microtubule regulators that relays cellular status information, such as cellular stress, to the integrity of microtubules in order to instruct neuroregeneration.


Assuntos
Anilidas/metabolismo , Axônios/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Ácidos Hidroxâmicos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Regeneração/genética , Animais , Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/genética , Ligação Proteica , Processamento de RNA/genética , Células Receptoras Sensoriais/fisiologia
9.
Toxicol Lett ; 320: 95-102, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760062

RESUMO

Exposure to organic solvent in industry, including n-hexane is correlated with central-peripheral axonopathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). However, the underlying mechanism is still largely unknown. Recently identified microRNAs (miRNAs) may play important roles in toxicant exposure and in the process of toxicant-induced neuropathys. To examine the role of miRNAs in HD-induced toxicity, neuropathic animal model was successfully built. miRNA microarray analysis revealed 105 differentially expressed miRNAs after HD exposure. Bioinformatics analysis showed that "Axon" and "Neurotrophin Signaling Pathway" was the top significant GO term and pathway, respectively. 7 miRNAs both related to "Axon" and "Neurotrophin Signaling Pathway" were screened out and further confirmed by Real-Time PCR. Correspondingly, the deregulation expression levels of proteins of four target genes (GSK3ß, Map3k1, BDNF and MAP1B) were further confirmed via western blot, verifying the results of gene target analysis. Taken together, our results showed that the axon-related miRNAs to be associated with MAP1B or neurotrophin signal pathways changed in nerve tissues following HD exposure. These miRNAs may play important roles in HD-induced neurotoxicity.


Assuntos
Axônios/efeitos dos fármacos , Hexanonas/toxicidade , MicroRNAs/metabolismo , Síndromes Neurotóxicas/etiologia , Nervo Isquiático/efeitos dos fármacos , Solventes/toxicidade , Medula Espinal/efeitos dos fármacos , Animais , Axônios/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Bases de Dados Genéticas , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , MAP Quinase Quinase Quinase 1/genética , MAP Quinase Quinase Quinase 1/metabolismo , Masculino , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Transcriptoma
10.
Life Sci ; 240: 117085, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759042

RESUMO

AIMS: Our study was designed to explore the function and mechanism of Tanshinone IIA in alleviating pain syndrome caused by endometriosis (EMs). MAIN METHODS: Female Sprague-Dawley rats went through autotransplantation operation to establish EMs model. The rats were randomly divided into five groups: sham, model, positive, Tanshinone IIA (L) (3 mg/kg/d) and Tanshinone IIA (H) (12 mg/kg/d) group. Volume of ectopic endometrium was measured after 21 days of continuous administration. Serum estradiol (E2) was detected by enzyme linked immunosorbent assay (Elisa). The protein expression of angiotensinogen (AGT), renin (REN), angiotensin converting enzyme (ACE), angiotensin II (ANGII) and angiotensin II type 2 receptor (AT2) in the dorsal root ganglion (DRG) neurons were measured by immunohistochemistry and Western Blotting. The mRNA expression levels of AGT and ANGII were measured by Real-time polymerase chain reaction (PCR). KEY FINDINGS: Tissue measurements showed that tanshinone IIA significantly inhibited the growth of ectopic endometrium. Tanshinone IIA could improve the paw withdrawal threshold thus reducing the mechanical hyperalgesia of EMs rats. Moreover, Tanshinone IIA regulated the DRG renin angiotensin system (RAS) by reducing the protein expression of AGT, REN, ACE, ANGII and AT2 in DRG neurons. Furthermore, Real-time PCR results also showed that the mRNA expression levels of AGT and ANGII in the DRG neurons were decreased. SIGNIFICANCE: The Tanshinone IIA inhibitory effect on the EMs associated pain in EMs rats might occur through decreasing the expression of E2, ANGII and AT2, thus halting DRG sprouting and promoting hyperalgesia threshold.


Assuntos
/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Axônios/patologia , Endometriose/tratamento farmacológico , Gânglios Espinais/patologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Endometriose/patologia , Estradiol/metabolismo , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Ratos , Ratos Sprague-Dawley
11.
Cell Mol Life Sci ; 77(1): 161-177, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31161284

RESUMO

Peripheral nervous system development involves a tight coordination of neuronal birth and death and a substantial remodelling of the myelinating glia cytoskeleton to achieve myelin wrapping of its projecting axons. However, how these processes are coordinated through time is still not understood. We have identified engulfment and cell motility 1, Elmo1, as a novel component that regulates (i) neuronal numbers within the Posterior Lateral Line ganglion and (ii) radial sorting of axons by Schwann cells (SC) and myelination in the PLL system in zebrafish. Our results show that neuronal and myelination defects observed in elmo1 mutant are rescued through small GTPase Rac1 activation. Inhibiting macrophage development leads to a decrease in neuronal numbers, while peripheral myelination is intact. However, elmo1 mutants do not show defective macrophage activity, suggesting a role for Elmo1 in PLLg neuronal development and SC myelination independent of macrophages. Forcing early Elmo1 and Rac1 expression specifically within SCs rescues elmo1-/- myelination defects, highlighting an autonomous role for Elmo1 and Rac1 in radial sorting of axons by SCs and myelination. This uncovers a previously unknown function of Elmo1 that regulates fundamental aspects of PNS development.


Assuntos
Bainha de Mielina/metabolismo , Neurogênese , Neurônios/citologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Apoptose , Axônios/metabolismo , Axônios/ultraestrutura , Movimento Celular , Neurônios/metabolismo , Neurônios/ultraestrutura , Nervos Periféricos/crescimento & desenvolvimento , Nervos Periféricos/ultraestrutura , Células de Schwann/citologia , Células de Schwann/metabolismo , Células de Schwann/ultraestrutura
12.
J Colloid Interface Sci ; 559: 65-75, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610306

RESUMO

Electroactive nanofibrous scaffold is a vital tool for the study of the various biological research fields from bioelectronics to regenerative medicine, which can provide cell preferable 3D nanofiber architecture and programmed electrical signal. However, intrinsic non-biodegradability is a major problem that hinders its widespread application in the clinic. Herein, we designed, synthesized, and characterized shell/core poly (3,4-ethylenedioxythiophene) (PEDOT)/chitosan (CS) nanofibers by combining the electrospinning and recrystallization processes. Upon incorporating a trace amount of PEDOT (1.0 wt%), the resultant PEDOT/CS nanofibers exhibited low interfacial charge transfer impedance, high electrochemical stability, high electrical conductivity (up to 0.1945 S/cm), and ultrasensitive piezoelectric property (output voltage of 22.5 mV by a human hair prodding). With such unique electrical and conductive properties, PEDOT/CS nanofibers were further applied to brain neuroglioma cells (BNCs) to stimulate their adhesion, proliferation, growth, and development under an optimal external electrical stimulation (ES) and a pulse voltage of 400 mV/cm. ES-responsive PEDOT/CS nanofibers indeed promoted BNCs growth and development as indicated by a large number and density of axons. The synergetic interplay between external ES and piezoelectric voltage demonstrates new PEDOT-based nanofibers as implantable electroactive scaffolds for numerous applications in nerve tissue engineering, human health monitoring, brain mantle information extraction, and degradable microelectronic devices.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Quitosana/química , Condutividade Elétrica , Nanofibras/química , Polímeros/química , Testes de Impedância Acústica/métodos , Axônios/metabolismo , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalização , Estimulação Elétrica/métodos , Glioma/metabolismo , Humanos
13.
Nat Commun ; 10(1): 5504, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796741

RESUMO

3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.


Assuntos
Conectoma , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Microscopia , Animais , Automação , Axônios/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Software , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
14.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31885862

RESUMO

Emerging data point to important contributions of both autoimmune inflammation and progressive degeneration in the pathophysiology of multiple sclerosis (MS). Unfortunately, after decades of intensive investigation, the fundamental cause remains unknown. A large body of research on the immunobiology of MS has resulted in a variety of anti-inflammatory therapies that are highly effective at reducing brain inflammation and clinical/radiological relapses. However, despite potent suppression of inflammation, benefit in the more important and disabling progressive phase is extremely limited; thus, progressive MS has emerged as the greatest challenge for the MS research and clinical communities. Data obtained over the years point to a complex interplay between environment (e.g., the near-absolute requirement of Epstein-Barr virus exposure), immunogenetics (strong associations with a large number of immune genes), and an ever more convincing role of an underlying degenerative process resulting in demyelination (in both white and grey matter regions), axonal and neuro-synaptic injury, and a persistent innate inflammatory response with a seemingly diminishing role of T cell-mediated autoimmunity as the disease progresses. Together, these observations point toward a primary degenerative process, one whose cause remains unknown but one that entrains a nearly ubiquitous secondary autoimmune response, as a likely sequence of events underpinning this disease. Here, we briefly review what is known about the potential pathophysiological mechanisms, focus on progressive MS, and discuss the two main hypotheses of MS pathogenesis that are the topic of vigorous debate in the field: whether primary autoimmunity or degeneration lies at the foundation. Unravelling this controversy will be critically important for developing effective new therapies for the most disabling later phases of this disease.


Assuntos
Doenças Desmielinizantes , Encefalite , Esclerose Múltipla , Axônios , Substância Cinzenta , Humanos
15.
Yakugaku Zasshi ; 139(11): 1385-1390, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31685734

RESUMO

In neurodegenerative diseases, such as Alzheimer's disease (AD) and spinal cord injury (SCI), inhibited axonal regeneration lead to irreversible functional impairment. Although many agents that eliminate axonal growth impediments have been clinically investigated, none induced functional recovery. I hypothesized that the removal of impediments alone was not enough and that promoting axonal growth and neuronal network reconstruction were needed for recovery from neurodegenerative diseases. To promote axonal growth, I have focused on neurons and microglia. In vitro models of AD and SCI were developed by culturing neurons in the presence of amyloid ß (Aß) and chondroitin sulfate proteoglycan, respectively. These were then used to identify several extracts of herbal medicines and their constituents that promoted axonal growth. Oral administration of these extracts and their constituents improved memory and motor function in in vivo mouse models of AD and SCI, respectively. The bioactive compounds in these extracts were identified by analyzing brain and spinal cord samples from the mice. Their protein targets were identified using the drug affinity responsive target stability method. Analysis of early events in the axons after culture with Aß revealed that the inhibition of endocytosis was sufficient to prevent the axonal atrophy and memory deficits caused by Aß. The compounds that increased M2 microglia were observed to promote axonal normalization and growth; they were also found to recover memory and motor function in mice models of AD and SCI, respectively. The above results indicate that axonal growth plays important roles in the recovery from AD and SCI.


Assuntos
Axônios/fisiologia , Medicina Herbária , Regeneração Nervosa , Doenças Neurodegenerativas/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Endocitose/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Estimulação Química
16.
Curr Opin Neurobiol ; 59: 213-220, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31710891

RESUMO

The assembly of functional neural circuits in vertebrate organisms requires complex mechanisms of self-recognition and self-avoidance. Neurites (axons and dendrites) from the same neuron recognize and avoid self, but engage in synaptic interactions with other neurons. Vertebrate neural self-avoidance requires the expression of distinct repertoires of clustered Protocadherin (Pcdh) cell-surface protein isoforms, which act as cell-surface molecular barcodes that mediate highly specific homophilic self-recognition, followed by repulsion. The generation of sufficiently diverse cell-surface barcodes is achieved by the stochastic and combinatorial activation of a subset of clustered Pcdh promoters in individual neurons. This remarkable mechanism leads to the generation of enormous molecular diversity at the cell surface. Here we review recent studies showing that stochastic expression of individual Pcdhα isoforms is accomplished through an extraordinary mechanism involving the activation of 'antisense strand' promoter within Pcdhα 'variable' exons, antisense transcription of a long non-coding RNA through the upstream 'sense strand' promoter, demethylation of this promoter, binding of the CTCF/cohesin complex and DNA looping to a distant enhancer through a mechanism of chromatin 'extrusion'.


Assuntos
Neurônios , Axônios , Caderinas , Dendritos , Isoformas de Proteínas
17.
Adv Neurobiol ; 23: 347-361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31667815

RESUMO

The astrocyte-neuron lactate transfer shuttle (ANLS) is one of the important metabolic systems that provides a physiological infrastructure for glia-neuronal interactions where specialized architectural organization supports the function. Perivascular astrocyte end-feet take up glucose via glucose transporter 1 to actively regulate glycogen stores, such that high ambient glucose upregulates glycogen and low levels of glucose deplete glycogen stores. A rapid breakdown of glycogen into lactate during increased neuronal activity or low glucose conditions becomes essential for maintaining axon function. However, it fails to benefit axon function during an ischemic episode in white matter (WM). Aging causes a remarkable change in astrocyte architecture characterized by thicker, larger processes oriented parallel to axons, as opposed to vertically-transposing processes. Subsequently, aging axons become more vulnerable to depleted glycogen, although aging axons can use lactate as efficiently as young axons. Lactate equally supports function during aglycemia in corpus callosum (CC), which consists of a mixture of myelinated and unmyelinated axons. Moreover, axon function in CC shows greater resilience to a lack of glucose compared to optic nerve, although both WM tracts show identical recovery after aglycemic injury. Interestingly, emerging evidence implies that a lactate transport system is not exclusive to astrocytes, as oligodendrocytes support the axons they myelinate, suggesting another metabolic coupling pathway in WM. Future studies are expected to unravel the details of oligodendrocyte-axon lactate metabolic coupling to establish that all WM components metabolically cooperate and that lactate may be the universal metabolite to sustain central nervous system function.


Assuntos
Envelhecimento/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Encéfalo/citologia , Encéfalo/metabolismo , Comunicação Celular , Glicogênio/metabolismo , Ácido Láctico/metabolismo , Axônios/metabolismo , Encéfalo/patologia , Glucose/metabolismo , Oligodendroglia/metabolismo
18.
Brain Nerve ; 71(11): 1169-1181, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31722303

RESUMO

Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. Riluzole and edaravone are the only approved drugs available in Japan to date. Approximately 10% of ALS cases are familial in rature, defined as the existence of disease-causing mutation. SOD1 is the most frequent causative gene for ALS among Japanese individuals, while C9orf72 mutation is more prevalent in Western countries. Genotype-phenotype correlation described in the literature of familial ALS enables to establish models of the disease. This review article describes the clinical characteristics of familial ALS based on each disease-causing mutation. The pathomechanism of ALS including proteostasis, RNA metabolism, and axonal pathology are discussed in detail. We also reviewed the status of development of therapeutic strategies for familial ALS based on analysis of animal models and induced pluripotent stem cells.


Assuntos
Esclerose Amiotrófica Lateral/genética , Adulto , Esclerose Amiotrófica Lateral/terapia , Animais , Axônios/patologia , Proteína C9orf72/genética , Modelos Animais de Doenças , Humanos , Células-Tronco Pluripotentes Induzidas , Japão , Neurônios Motores/patologia , Mutação , Superóxido Dismutase-1/genética
20.
Adv Exp Med Biol ; 1190: 43-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760637

RESUMO

Oligodendrocyte form myelin around the axons to regulate the conduction velocity. Myelinated axons are composed of white matter to act as cables to connect distinct brain regions. Recent human MRI studies showed that the signal from white matter change in the people with special skills such as taxi driver, piano player, and juggling. The change of the white matter suggested that (1) The plasticity of myelination depends on neuronal activity (activity-dependent myelination) and (2) White matter plasticity is essential for brain functions. In this session, we discussed that how the un-electrical components, oligodendrocytes, and its precursor cells receive the signal from electrically active neurons and differentiate, proliferate, and myelinate the axons to modulate the activity of neuronal circuits, ultimately affect on their behaviors. In this review, we highlight the physiological functions of oligodendrocyte and their neuronal activity-dependent functions and thus show new insight for their contribution to brain functions.


Assuntos
Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Substância Branca/fisiologia , Axônios/fisiologia , Humanos , Neurônios/fisiologia
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