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1.
Immunity ; 54(10): 2194-2208, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644556

RESUMO

As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.


Assuntos
Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Homeostase/fisiologia , Microglia/citologia , Microglia/fisiologia , Animais , Humanos
2.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34639067

RESUMO

All eukaryotic cells are composed of the cytoskeleton, which plays crucial roles in coordinating diverse cellular functions such as cell division, morphology, migration, macromolecular stabilization, and protein trafficking. The cytoskeleton consists of microtubules, intermediate filaments, and actin filaments. Cofilin, an actin-depolymerizing protein, is indispensable for regulating actin dynamics in the central nervous system (CNS) development and function. Cofilin activities are spatiotemporally orchestrated by numerous extra- and intra-cellular factors. Phosphorylation at Ser-3 by kinases attenuate cofilin's actin-binding activity. In contrast, dephosphorylation at Ser-3 enhances cofilin-induced actin depolymerization. Cofilin functions are also modulated by various binding partners or reactive oxygen species. Although the mechanism of cofilin-mediated actin dynamics has been known for decades, recent research works are unveiling the profound impacts of cofilin dysregulation in neurodegenerative pathophysiology. For instance, oxidative stress-induced increase in cofilin dephosphorylation is linked to the accumulation of tau tangles and amyloid-beta plaques in Alzheimer's disease. In Parkinson's disease, cofilin activation by silencing its upstream kinases increases α-synuclein-fibril entry into the cell. This review describes the molecular mechanism of cofilin-mediated actin dynamics and provides an overview of cofilin's importance in CNS physiology and pathophysiology.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Sistema Nervoso Central/fisiologia , Suscetibilidade a Doenças , Degeneração Neural/etiologia , Degeneração Neural/metabolismo , Transdução de Sinais , Fatores de Despolimerização de Actina/genética , Animais , Axônios/metabolismo , Proteínas de Transporte/metabolismo , Humanos , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Família Multigênica , Degeneração Neural/patologia , Regeneração Nervosa , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Plasticidade Neuronal , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo
3.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575969

RESUMO

A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.


Assuntos
Encéfalo/fisiologia , Sistema Nervoso Central/fisiologia , Plasticidade Neuronal/fisiologia , Núcleo Accumbens/fisiologia , Animais , Humanos , Satisfação Pessoal , Recompensa
4.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502395

RESUMO

Stroke disrupts the homeostatic balance within the brain and is associated with a significant accumulation of necrotic cellular debris, fluid, and peripheral immune cells in the central nervous system (CNS). Additionally, cells, antigens, and other factors exit the brain into the periphery via damaged blood-brain barrier cells, glymphatic transport mechanisms, and lymphatic vessels, which dramatically influence the systemic immune response and lead to complex neuroimmune communication. As a result, the immunological response after stroke is a highly dynamic event that involves communication between multiple organ systems and cell types, with significant consequences on not only the initial stroke tissue injury but long-term recovery in the CNS. In this review, we discuss the complex immunological and physiological interactions that occur after stroke with a focus on how the peripheral immune system and CNS communicate to regulate post-stroke brain homeostasis. First, we discuss the post-stroke immune cascade across different contexts as well as homeostatic regulation within the brain. Then, we focus on the lymphatic vessels surrounding the brain and their ability to coordinate both immune response and fluid homeostasis within the brain after stroke. Finally, we discuss how therapeutic manipulation of peripheral systems may provide new mechanisms to treat stroke injury.


Assuntos
Neuroimunomodulação/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Animais , Transporte Biológico , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/fisiologia , Homeostase , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Imunidade , Leucócitos , Linfangiogênese , Vasos Linfáticos , Neuroimunomodulação/fisiologia
5.
Nat Rev Neurosci ; 22(11): 657-673, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34545240

RESUMO

Almost 60 years have passed since the initial discovery by Hubel and Wiesel that changes in neuronal activity can elicit developmental rewiring of the central nervous system (CNS). Over this period, we have gained a more comprehensive picture of how both spontaneous neural activity and sensory experience-induced changes in neuronal activity guide CNS circuit development. Here we review activity-dependent synaptic pruning in the mammalian CNS, which we define as the removal of a subset of synapses, while others are maintained, in response to changes in neural activity in the developing nervous system. We discuss the mounting evidence that immune and cell-death molecules are important mechanistic links by which changes in neural activity guide the pruning of specific synapses, emphasizing the role of glial cells in this process. Finally, we discuss how these developmental pruning programmes may go awry in neurodevelopmental disorders of the human CNS, focusing on autism spectrum disorder and schizophrenia. Together, our aim is to give an overview of how the field of activity-dependent pruning research has evolved, led to exciting new questions and guided the identification of new, therapeutically relevant mechanisms that result in aberrant circuit development in neurodevelopmental disorders.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Sistema Nervoso Central/fisiologia , Imunidade Celular/fisiologia , Plasticidade Neuronal/fisiologia , Esquizofrenia/fisiopatologia , Fatores Etários , Animais , Transtorno do Espectro Autista/imunologia , Sistema Nervoso Central/citologia , Humanos , Transtornos do Neurodesenvolvimento/imunologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Esquizofrenia/imunologia
6.
Nutrients ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34444663

RESUMO

Caffeine is one of the most consumed ergogenic aids around the world. Many studies support the ergogenic effect of caffeine over a large spectrum of exercise types. While the stimulatory effect of caffeine on the central nervous system is the well-accepted mechanism explaining improvements in exercise performance during high-intensity whole-body exercise, in which other physiological systems such as pulmonary, cardiovascular, and muscular systems are maximally activated, a direct effect of caffeine on such systems cannot be ignored. A better understanding of the effects of caffeine on multiple physiological systems during high-intensity whole-body exercise might help to expand its use in different sporting contexts (e.g., competitions in different environments, such as altitude) or even assist the treatment of some diseases (e.g., chronic obstructive pulmonary disease). In the present narrative review, we explore the potential effects of caffeine on the pulmonary, cardiovascular, and muscular systems, and describe how such alterations may interact and thus contribute to the ergogenic effects of caffeine during high-intensity whole-body exercise. This integrative approach provides insights regarding how caffeine influences endurance performance and may drive further studies exploring its mechanisms of action in a broader perspective.


Assuntos
Cafeína/farmacologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Exercício Físico/fisiologia , Pulmão/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/farmacologia , Resistência Física/efeitos dos fármacos , Animais , Sistema Nervoso Central/fisiologia , Humanos , Pulmão/fisiologia , Músculo Esquelético/fisiologia
7.
Brain Pathol ; 31(6): e13013, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34390282

RESUMO

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared with its well-known pulmonary tropism and respiratory complications, little has been studied about SARS-CoV-2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID-19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID-19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS-CoV-2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID-19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID-19 should be included in a protocol of standardized criteria to perform autopsies on these subjects.


Assuntos
Encéfalo/fisiologia , Encéfalo/virologia , COVID-19/patologia , Doenças do Sistema Nervoso/virologia , SARS-CoV-2/metabolismo , Encéfalo/fisiopatologia , COVID-19/metabolismo , COVID-19/virologia , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/virologia , Humanos , Inflamação/patologia , Inflamação/virologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/patologia , Pandemias
8.
Zool Res ; 42(4): 478-481, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213094

RESUMO

Tree shrews (Tupaia spp.) have been used in neuroscience research since the 1960s due to their evolutionary proximity to primates. The use and interest in this animal model have recently increased, in part due to the adaptation of modern neuroscience tools in this species. These tools include quantitative behavioral assays, calcium imaging, optogenetics and transgenics. To facilitate the exchange and development of these new technologies and associated research findings, we organized the inaugural "Tree Shrew Users Meeting" which was held online due to the COVID-19 pandemic. Here, we review this meeting and discuss the history of tree shrews as an animal model in neuroscience research and summarize the current themes being investigated using this animal, as well as future directions.


Assuntos
Sistema Nervoso Central/fisiologia , Modelos Animais de Doenças , Tupaiidae , Animais , Pesquisa Biomédica/métodos
9.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34083450

RESUMO

The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis. B cells reach the meninges from the calvaria through specialized vascular connections. This calvarial-meningeal path of B cell development may provide the CNS with a constant supply of B cells educated by CNS antigens. Conversely, we show that a subset of antigen-experienced B cells that populate the meninges in aging mice are blood-borne. These results identify a private source for meningeal B cells, which may help maintain immune privilege within the CNS.


Assuntos
Subpopulações de Linfócitos B/fisiologia , Linfócitos B/fisiologia , Células da Medula Óssea/fisiologia , Sistema Nervoso Central/imunologia , Dura-Máter/citologia , Linfopoese , Meninges/citologia , Meninges/imunologia , Crânio/anatomia & histologia , Envelhecimento , Animais , Subpopulações de Linfócitos B/imunologia , Movimento Celular , Sistema Nervoso Central/fisiologia , Dura-Máter/imunologia , Fibroblastos/fisiologia , Homeostase , Privilégio Imunológico , Camundongos , Plasmócitos/fisiologia , Análise de Célula Única
10.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070424

RESUMO

BACKGROUND: The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning. AIMS: To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function. CONCLUSIONS: This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.


Assuntos
Sistema Nervoso Central/metabolismo , Matriz Extracelular/metabolismo , Rede Nervosa/metabolismo , Neurônios/metabolismo , Sistema Nervoso Periférico/metabolismo , Animais , Sistema Nervoso Central/enzimologia , Sistema Nervoso Central/fisiologia , Humanos , Ácido Hialurônico/metabolismo , Rede Nervosa/enzimologia , Rede Nervosa/fisiologia , Neurogênese/genética , Neurogênese/fisiologia , Sistema Nervoso Periférico/enzimologia , Sistema Nervoso Periférico/fisiologia , Proteoglicanas/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
11.
Front Immunol ; 12: 666961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936108

RESUMO

In multiple sclerosis (MS) and other neuroinflammatory diseases, monocyte-derived cells (MoCs) traffic through distinct central nervous system (CNS) barriers and gain access to the organ parenchyma exerting detrimental or beneficial functions. How and where these MoCs acquire their different functional commitments during CNS invasion remains however unclear, thus hindering the design of MS treatments specifically blocking detrimental MoC actions. To clarify this issue, we investigated the distribution of iNOS+ pro-inflammatory and arginase-1+ anti-inflammatory MoCs at the distinct border regions of the CNS in a mouse model of MS. Interestingly, MoCs within perivascular parenchymal spaces displayed a predominant pro-inflammatory phenotype compared to MoCs accumulating at the leptomeninges and at the intraventricular choroid plexus (ChP). Furthermore, in an in vitro model, we could observe the general ability of functionally-polarized MoCs to migrate through the ChP epithelial barrier, together indicating the ChP as a potential CNS entry and polarization site for MoCs. Thus, pro- and anti-inflammatory MoCs differentially accumulate at distinct CNS barriers before reaching the parenchyma, but the mechanism for their phenotype acquisition remains undefined. Shedding light on this process, we observed that endothelial (BBB) and epithelial (ChP) CNS barrier cells can directly regulate transcription of Nos2 (coding for iNOS) and Arg1 (coding for arginase-1) in interacting MoCs. More specifically, while TNF-α+IFN-γ stimulated BBB cells induced Nos2 expression in MoCs, IL-1ß driven activation of endothelial BBB cells led to a significant upregulation of Arg1 in MoCs. Supporting this latter finding, less pro-inflammatory MoCs could be found nearby IL1R1+ vessels in the mouse spinal cord upon neuroinflammation. Taken together, our data indicate differential distribution of pro- and anti-inflammatory MoCs at CNS borders and highlight how the interaction of MoCs with CNS barriers can significantly affect the functional activation of these CNS-invading MoCs during autoimmune inflammation.


Assuntos
Arginase/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Macrófagos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/fisiopatologia , Células Endoteliais/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/metabolismo , Esclerose Múltipla/fisiopatologia
12.
Elife ; 102021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973523

RESUMO

The mechanisms specifying neuronal diversity are well characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts) and identify them in a synapse-scale TEM reconstruction of the Drosophila larval central nervous system. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.


Assuntos
Sistema Nervoso Central/fisiologia , Drosophila melanogaster/fisiologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Animais , Proteínas de Drosophila/fisiologia
13.
Chem Senses ; 462021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34003211

RESUMO

Newborns have a functioning sense of smell at birth, which appears to be highly significant for feeding and bonding. Still, little is known about the cerebral odor processing in this age group. Studies of olfactory function relied mostly on behavioral, autonomic, and facial responses of infants. The aim of the present study was to investigate central odor processing in infants focusing on electroencephalography (EEG)-derived responses to biologically significant odors, namely a food and a non-food odor. A total of 21 term-born, healthy infants participated (11 boys and 10 girls; age range 2-9 months, mean 5.3 ± 2.2 months). Odor stimuli were presented using a computer-controlled olfactometer. Breast milk was used as food odor. Farnesol was presented as a non-food odor. In addition, odorless air was used as a control stimulus. Each stimulus was presented 30 times for 1 s with an interstimulus interval of 20 s. EEG was recorded from 9 electrodes and analyzed in the frequency domain. EEG amplitudes in the delta frequency band differed significantly after presentation of food (breast milk) odor in comparison to the control condition and the non-food odor (farnesol). These changes were observed at the frontal recording positions. The present study indicates that central odor processing differs between a food and a non-food odor in infants. Results are interpreted in terms of focused attention towards a physiologically relevant odor (breast milk), suggesting that olfactory stimuli are of specific significance in this age group.


Assuntos
Sistema Nervoso Central/fisiologia , Leite Humano/química , Odorantes , Olfato/fisiologia , Feminino , Humanos , Lactente , Masculino , Mães
14.
Nat Commun ; 12(1): 3020, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021144

RESUMO

Stem cell technologies including self-assembling 3D tissue models provide access to early human neurodevelopment and fundamental insights into neuropathologies. Gastruloid models have not been used to investigate co-developing central and peripheral neuronal systems with trunk mesendoderm which we achieve here in elongating multi-lineage organized (EMLO) gastruloids. We evaluate EMLOs over a forty-day period, applying immunofluorescence of multi-lineage and functional biomarkers, including day 16 single-cell RNA-Seq, and evaluation of ectodermal and non-ectodermal neural crest cells (NCCs). We identify NCCs that differentiate to form peripheral neurons integrated with an upstream spinal cord region after day 8. This follows initial EMLO polarization events that coordinate with endoderm differentiation and primitive gut tube formation during multicellular spatial reorganization. This combined human central-peripheral nervous system model of early organogenesis highlights developmental events of mesendoderm and neuromuscular trunk regions and enables systemic studies of tissue interactions and innervation of neuromuscular, enteric and cardiac relevance.


Assuntos
Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Sistema Nervoso Periférico/citologia , Sistema Nervoso Periférico/patologia , Biomarcadores , Diferenciação Celular/fisiologia , Fatores de Transcrição Forkhead , Expressão Gênica , Humanos , Morfogênese , Crista Neural , Fenótipo , Fatores de Transcrição SOXE , Fator de Transcrição AP-2
15.
Hum Mov Sci ; 77: 102798, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33857702

RESUMO

Humans readily entrain their movements to a beat, including matching their gait to a prescribed tempo. Rhythmic auditory cueing tasks have been used to enhance stepping behavior in a variety of clinical populations. However, there is limited understanding of how temporal accuracy of gait changes over practice in healthy young adults. In this study, we examined how inter-step interval and cadence deviated from slow, medium, and fast tempos across steps within trials, across trials within blocks, and across two blocks that bookended a period of practice of walking to each tempo. Participants were accurate in matching the tempo at the slow and medium tempos, while they tended to lag behind the beat at the fast tempo. We also found that participants showed no substantial improvement across steps and trials, nor across blocks, suggesting that participants had a robust ability to entrain their gait to the specified metronome tempo. However, we did find that participants habituated to the prescribed tempo, showing self-paced gait that was faster than self-paced baseline gait after the fast tempo, and slower than self-paced baseline gait after the slow tempo. These findings might represent an "after-effect" in the temporal domain, akin to after-effects consistently shown in other sensorimotor tasks. This knowledge of how healthy participants entrain their gait to temporal cues may have important implications in understanding how clinical populations acquire and modify their gait in rhythmic auditory cueing tasks.


Assuntos
Estimulação Acústica , Marcha/fisiologia , Caminhada/fisiologia , Adulto , Antropometria , Sistema Nervoso Central/fisiologia , Sinais (Psicologia) , Nível de Saúde , Voluntários Saudáveis , Audição , Humanos , Masculino , Prática Psicológica , Reprodutibilidade dos Testes , Adulto Jovem
16.
PLoS One ; 16(4): e0244902, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857131

RESUMO

Intercellular gap junction channels and single-membrane channels have been reported to regulate electrical synapse and the brain function. Innexin is known as a gap junction-related protein in invertebrates and is involved in the formation of intercellular gap junction channels and single-cell membrane channels. Multiple isoforms of innexin protein in each species enable the precise regulation of channel function. In molluscan species, sequence information of innexins is still limited and the sequences of multiple innexin isoforms have not been classified. This study examined the innexin transcripts expressed in the central nervous system of the terrestrial slug Limax valentianus and identified 16 transcripts of 12 innexin isoforms, including the splicing variants. We performed phylogenetic analysis and classified the isoforms with other molluscan innexin sequences. Next, the phosphorylation, N-glycosylation, and S-nitrosylation sites were predicted to characterize the innexin isoforms. Further, we identified 16 circular RNA sequences of nine innexin isoforms in the central nervous system of Limax. The identification and classification of molluscan innexin isoforms provided novel insights for understanding the regulatory mechanism of innexin in this phylum.


Assuntos
Conexinas/classificação , Conexinas/genética , Gastrópodes/genética , Animais , Transporte Biológico/fisiologia , Sistema Nervoso Central/fisiologia , Sinapses Elétricas/metabolismo , Junções Comunicantes/genética , Junções Comunicantes/metabolismo , Gastrópodes/metabolismo , Expressão Gênica/genética , Canais Iônicos/metabolismo , Filogenia , Isoformas de Proteínas/genética , Transcriptoma/genética
17.
Knee ; 30: 78-89, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33873089

RESUMO

BACKGROUND: Despite surgical reconstruction and extensive rehabilitation, persistent quadriceps inhibition, gait asymmetry, and functional impairment remain prevalent in patients after anterior cruciate ligament (ACL) injury. A combination of reports have suggested underlying central nervous system adaptations in those after injury govern long-term neuromuscular impairments. The classic assumption has been to attribute neurophysiologic deficits to components of injury, but other factors across the continuum of care (e.g. surgery, perioperative analgesia, and rehabilitative strategies) have been largely overlooked. OBJECTIVE: This review provides a multidisciplinary perspective to 1) provide a narrative review of studies reporting neuroplasticity following ACL injury in order to inform clinicians of the current state of literature and 2) provide a mechanistic framework of neurophysiologic deficits with potential clinical implications across all phases of injury and recovery (injury, surgery, and rehabilitation) RESULTS: Studies using a variety of neurophysiologic modalities have demonstrated peripheral and central nervous system adaptations in those with prior ACL injury. Longitudinal investigations suggest neurophysiologic changes at spinal-reflexive and corticospinal pathways follow a unique timecourse across injury, surgery, and rehabilitation. CONCLUSION: Clinicians should consider the unique injury, surgery, anesthesia, and rehabilitation on central nervous system adaptations. Therapeutic strategies across the continuum of care may be beneficial to mitigate maladaptive neuroplasticity in those after ACL injury.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Reconstrução do Ligamento Cruzado Anterior/reabilitação , Sistema Nervoso Central/fisiologia , Ruptura/reabilitação , Adaptação Fisiológica , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/reabilitação , Sistema Nervoso Central/fisiopatologia , Potenciais Somatossensoriais Evocados , Marcha , Humanos , Bloqueio Nervoso/métodos , Neuroimagem , Músculo Quadríceps/fisiopatologia , Ruptura/cirurgia
18.
Med Sci Monit ; 27: e929609, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33879761

RESUMO

BACKGROUND A lack of physical exercise, a critical aspect of a healthy lifestyle, contributes to several cerebral diseases, such as cognitive impairment, Parkinson disease (PD), and Alzheimer disease (AD). The purpose of the present study was to evaluate the effect of physical exercise on cerebral disease via released extracellular vesicles (EVs). MATERIAL AND METHODS Short-term high-intensity treadmill exercise was applied to assess the effect of physical activity on EVs in the serum and brain tissue. Immunofluorescence staining and western blot analysis were used to analyze biomarkers of EVs, including TSG101, HSC70, and CD63. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of EVs. RESULTS Short-term high-intensity exercise increased the number of neuronal EVs in the brain. In the peripheral blood serum, the level of HSC70 showed a temporary increase after exercise and quickly returned to the normal level, whereas the levels of CD63 and TSG101 showed no obvious change in response to physical exercise. In brain tissue, the levels of HSC70 and TSG101 increased dramatically after exercise, while the level of CD63 remained unchanged. The concentration of EVs was significantly increased after exercise, while the mean diameter of the EVs showed no significant change. The levels of ceramide were significantly increased after exercise, and quickly returned to normal levels. CONCLUSIONS These data suggest that the secretion of EVs in the brain and blood is a transitory response to physical exercise and is dependent on ceramide synthesis.


Assuntos
Encefalopatias/prevenção & controle , Sistema Nervoso Central/fisiologia , Vesículas Extracelulares/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Ceramidas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Teste de Esforço , Proteínas de Choque Térmico HSC70/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Tetraspanina 30/metabolismo , Fatores de Transcrição/metabolismo
19.
J Immunol Res ; 2021: 3258942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763490

RESUMO

Background: The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto's thyroiditis (HT) patients without central nervous system involvement. Methods: 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. Results: The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. Conclusions: There were changes in the brain's bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain's bioelectrical activity in the course of HT may be associated with an autoimmune process.


Assuntos
Encéfalo/fisiologia , Sistema Nervoso Central/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/imunologia , Doença de Hashimoto/fisiopatologia , Glândula Tireoide/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Encéfalo/diagnóstico por imagem , Ondas Encefálicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção Visual , Adulto Jovem
20.
Nat Commun ; 12(1): 1374, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654091

RESUMO

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.


Assuntos
Acetilcolina/metabolismo , Sistema Nervoso Central/fisiologia , Transmissão Sináptica/fisiologia , Células Amácrinas/fisiologia , Células Amácrinas/ultraestrutura , Animais , Dendritos/fisiologia , Dendritos/ultraestrutura , Cinética , Camundongos Endogâmicos C57BL , Fótons , Células Ganglionares da Retina/ultraestrutura
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