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1.
Adv Exp Med Biol ; 1131: 131-161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646509

RESUMO

Calcium (Ca2+) is a fundamental regulator of cell fate and intracellular Ca2+ homeostasis is crucial for proper function of the nerve cells. Given the complexity of neurons, a constellation of mechanisms finely tunes the intracellular Ca2+ signaling. We are focusing on the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) pump, an integral ER protein. SERCA's well established role is to preserve low cytosolic Ca2+ levels ([Ca2+]cyt), by pumping free Ca2+ ions into the ER lumen, utilizing ATP hydrolysis. The SERCA pumps are encoded by three distinct genes, SERCA1-3, resulting in 12 known protein isoforms, with tissue-dependent expression patterns. Despite the well-established structure and function of the SERCA pumps, their role in the central nervous system is not clear yet. Interestingly, SERCA-mediated Ca2+ dyshomeostasis has been associated with neuropathological conditions, such as bipolar disorder, schizophrenia, Parkinson's disease and Alzheimer's disease. We summarize here current evidence suggesting a role for SERCA in the neurobiology of neuropsychiatric and neurodegenerative disorders, thus highlighting the importance of this pump in brain physiology and pathophysiology.


Assuntos
Encéfalo , Retículo Endoplasmático , Doenças do Sistema Nervoso , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Encéfalo/enzimologia , Encéfalo/patologia , Retículo Endoplasmático/enzimologia , Regulação Enzimológica da Expressão Gênica , Homeostase , Humanos , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/fisiopatologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
2.
Toxicol Lett ; 315: 96-106, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386889

RESUMO

We investigate the long-term effect of very-low dose exposure to a mixture of six pesticides associated with hydrophilic vitamin deficiency on the neurobehavioral outcomes of rats. Two hundred Wistar rats were divided into four groups, two control groups, a vitamin sufficient control group and a vitamin deficiency control group and 2 test groups, a vitamin sufficient test group, and a vitamin deficiency group. The test groups were exposed for 9 months to a mixture of diquat, imazamox, imazethapyr, tepraloxydin, bentazone and acifluorfen in doses of 0.01xNOAEL (mg/kg bw/day). After 9 months of exposure, the behavior changes were evaluated by open field test and elevated plus maze test and the memory was assessed by passive avoidance test. Chronic vitamin deficiency decreased locomotor and special orientation activity and increased anxiety-like behavior in rats. Exposure to very low doses of a mixture of 6 pesticides caused central nervous effects, manifested as decreased locomotor activity, and increased anxiety levels. Vitamin deficiency and low dose chronic pesticides mixture exposure thus affected the central nervous system, especially long-term memory.


Assuntos
Deficiência de Vitaminas/complicações , Deficiência de Vitaminas/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/fisiopatologia , Praguicidas/toxicidade , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
3.
Sheng Li Xue Bao ; 71(4): 657-670, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440763

RESUMO

The neuropeptide orexin is widely distributed in the nervous system. Previous studies showed that orexin is involved in the feeding behavior regulation by binding to its receptor 1 (OX1R) and receptor 2 (OX2R) to activate the downstream signaling pathway. Recent studies have demonstrated that the system of orexin and its receptors are also involved in important physiological processes such as sleep-wake, learning and memory, and pathological processes of various neurological diseases. In this review, we summarized the research progress on the function of the orexin and its receptor system in physiological and pathological processes, and revealed the correlation between orexin and nervous system diseases, in order to provide the theoretical guidance for the diagnosis and treatment of the related diseases in the future.


Assuntos
Doenças do Sistema Nervoso/fisiopatologia , Receptores de Orexina/fisiologia , Orexinas/fisiologia , Humanos , Transdução de Sinais
4.
J Stroke Cerebrovasc Dis ; 28(9): 2459-2467, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31281111

RESUMO

BACKGROUND: The 10-meter Walking Test (10MWT) is often used to assess people with, e.g., stroke, but often using different procedures. The aims of this study were to translate the 10MWT into Danish, to determine the number of trials needed to achieve performance stability, and to examine the interrater reliability and agreement of the 10MWT in people with neurological disorders. METHODS: Translation followed international recommendations, and evaluated in a consecutive sample of 50 people with a neurological disorder. All participants performed 5 timed 10MWT trials (usual speed) with 20-seconds rest intervals between trials, supervised by a physical therapist. A second session was conducted with another physical therapist, separated with a mean (SD) of 2.7 (0.9) hours. The order of raters was randomized and they were blinded to each other's ratings. Repeated measures ANOVA determined performance stability, while ICC1.1, standard error of measurement (SEM), and minimal detectable change (MDC95) determined reproducibility. RESULTS: Participant's improved their 10MWT scores significantly between the first and second trial only. The faster of the 2 trials took a mean of 11.95 (5.40) seconds, and significantly (P < 0.001) faster than the slowest; mean of 12.80 (6.13) seconds. The intraclass correlation coefficient (ICC; 95% confidence interval), SEM, and MDC, based on the fastest of 2 trials, were 0.97 (0.95-0.98), 0.06 m/s, and 0.17 m/s, respectively, and with no systematic between rater's bias. CONCLUSIONS: We suggest that the faster of 2 timed trials be recorded for the 10MWT in people with neurological disorders, as we found excellent interrater reliability and low measurement error using this score.


Assuntos
Características Culturais , Tolerância ao Exercício , Doenças do Sistema Nervoso/diagnóstico , Tradução , Teste de Caminhada , Caminhada , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etnologia , Doenças do Sistema Nervoso/fisiopatologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Velocidade de Caminhada
5.
NeuroRehabilitation ; 44(3): 379-388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31227659

RESUMO

BACKGROUND: The interpretation of the verticality of the environment is crucial for a proper body balance. The subjective visual vertical test (SVV) is a widely used method to determine the visual perception of the verticality, whose alteration has been related with poor functional status. OBJECTIVE: To analyze the visual perception of the verticality in neurological patients in comparison with healthy controls. METHODS: We searched PubMed, Scopus, and Scielo from the start of the databases until October 2017 and manually searched the reference lists of studies comparing SVV values between neurological patients and controls. Standardized mean difference (SMD) and subgroup analysis were used to analyze differences between neurological patients and healthy subjects and between stroke and non-stroke patients, respectively. RESULTS: A total of 1,916 subjects from 31 studies were included. Neurological patients misestimate the true vertical in comparison with controls (SMD = 1.05; 95% CI: 0.81, 1.28). The misperception of the verticality was higher in stroke patients (SMD = 1.35; 95% CI: 1.02, 1.68) than in patients with other neurological conditions (SMD = 0.48; 95% CI: 0.29, 0.68). CONCLUSIONS: Neurological patients showed a misperception of the verticality, estimated using the SVV. The neurological pathology that most alters the SVV is stroke.


Assuntos
Equilíbrio Postural/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Percepção Visual/fisiologia , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia , Estudos Observacionais como Assunto/métodos , Acidente Vascular Cerebral/diagnóstico
6.
Sci Total Environ ; 678: 278-287, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075594

RESUMO

Groundwater, the major source of drinking water in Bengal Delta Plain, is contaminated with geogenic arsenic (As) enrichment affecting millions of people. Children exposed to tubewell water containing As may be associated with thyroid dysfunction, which in turn may impact neurodevelopmental outcomes. However, data to support such relationship is sparse. The purpose of this study was to examine if chronic water As (WAs) from Holocene alluvial aquifers in this region was associated with serum thyroid hormone (TH) and if TH biomarkers were related to neurobehavioral (NB) performance in a group of adolescents. A sample of 32 healthy adolescents were randomly drawn from a child cohort in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh. Half of these participants were consistently exposed to low WAs (<10 µg/L) and the remaining half had high WAs exposure (≥10 µg/L) since birth. Measurements included serum total triiodothyronine (tT3), free thyroxine (fT4), thyrotropin (TSH) and thyroperoxidase antibodies (TPOAb); concurrent WAs and urinary arsenic (UAs); and adolescents' NB performance. WAs and UAs were positively and significantly correlated with TPOAb but were not correlated with TSH, tT3 and fT4. After accounting for covariates, both WAs and UAs demonstrated positive but non-significant relationships with TSH and TPOAb and negative but non-significant relationships with tT3 and fT4. TPOAb was significantly associated with reduced NB performance indicated by positive associations with latencies in simple reaction time (b = 82.58; p < 0.001) and symbol digit (b = 276.85; p = 0.005) tests. TSH was significantly and negatively associated with match-to-sample correct count (b = -0.95; p = 0.05). Overall, we did not observe significant associations between arsenic exposure and TH biomarkers although the relationships were in the expected directions. We observed TH biomarkers to be related to reduced NB performance as hypothesized. Our study indicated a possible mechanism of As-induced neurotoxicity, which requires further investigations for confirmatory findings.


Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Arsênico/efeitos adversos , Doenças do Sistema Nervoso/fisiopatologia , Hormônios Tireóideos/sangue , Poluentes Químicos da Água/efeitos adversos , Adolescente , Bangladesh , Estudos de Coortes , Exposição Ambiental , Feminino , Humanos , Estudos Longitudinais , Masculino , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/induzido quimicamente , Projetos Piloto
7.
Middle East Afr J Ophthalmol ; 26(1): 37-39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114123

RESUMO

Marcus Gunn jaw-winking syndrome (MGJWS) is a rare form of congenital blepharoptosis and one of the congenital cranial dysinnervation disorders (CCDD). In addition, morning glory disc anomaly (MGDA) is a congenital optic disc anomaly of unknown etiology. The present report is the first to describe an association between MGJWS and MGDA in an otherwise healthy 7-year-old boy. He also had counting finger vision, anisometropia, esotropia, and monocular elevation deficiency in the same eye. In the literature, both MGJWS and MGDA have been reported to be associated with Duane retraction syndrome, a form of CCDD.


Assuntos
Blefaroptose/etiologia , Anormalidades do Olho/complicações , Cardiopatias Congênitas/etiologia , Anormalidades Maxilomandibulares/etiologia , Doenças do Sistema Nervoso/etiologia , Disco Óptico/anormalidades , Anisometropia/etiologia , Anisometropia/fisiopatologia , Blefaroptose/diagnóstico , Blefaroptose/fisiopatologia , Criança , Esotropia/etiologia , Esotropia/fisiopatologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Humanos , Anormalidades Maxilomandibulares/diagnóstico , Anormalidades Maxilomandibulares/fisiopatologia , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Reflexo Anormal
8.
Fluids Barriers CNS ; 16(1): 9, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30967147

RESUMO

The fine balance between the secretion, composition, volume and turnover of cerebrospinal fluid (CSF) is strictly regulated. However, during certain neurological diseases, this balance can be disrupted. A significant disruption to the normal CSF circulation can be life threatening, leading to increased intracranial pressure (ICP), and is implicated in hydrocephalus, idiopathic intracranial hypertension, brain trauma, brain tumours and stroke. Yet, the exact cellular, molecular and physiological mechanisms that contribute to altered hydrodynamic pathways in these diseases are poorly defined or hotly debated. The traditional views and concepts of CSF secretion, flow and drainage have been challenged, also due to recent findings suggesting more complex mechanisms of brain fluid dynamics than previously proposed. This review evaluates and summarises current hypotheses of CSF dynamics and presents evidence for the role of impaired CSF dynamics in elevated ICP, alongside discussion of the proteins that are potentially involved in altered CSF physiology during neurological disease. Undoubtedly CSF secretion, absorption and drainage are important aspects of brain fluid homeostasis in maintaining a stable ICP. Traditionally, pharmacological interventions or CSF drainage have been used to reduce ICP elevation due to over production of CSF. However, these drugs are used only as a temporary solution due to their undesirable side effects. Emerging evidence suggests that pharmacological targeting of aquaporins, transient receptor potential vanilloid type 4 (TRPV4), and the Na+-K+-2Cl- cotransporter (NKCC1) merit further investigation as potential targets in neurological diseases involving impaired brain fluid dynamics and elevated ICP.


Assuntos
Líquido Cefalorraquidiano , Hidrodinâmica , Pressão Intracraniana/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Animais , Humanos
10.
Med Hypotheses ; 125: 37-40, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30902149

RESUMO

Electroencephalogram (EEG) is one of the mechanisms used to collect complex data. Its use includes evaluating neurological disorders, investigating brain function and correlations between EEG signals and real or imagined movements. The Topographic Image of Cortical Activity (TICA) records obtained by the EEG make it possible to observe, through color discrimination, the cortical areas that represent greater or lesser activity. Percolation Theory (PT) reveals properties on the aspects of fluid spreading from a central point, these properties being related to the aspects of the medium, topological characteristics and ease of penetration of a fluid in materials. The hypothesis presented so far considers that synaptic activities originate in points and spread from them, causing different areas of the brain to interact in a diffusive associative behavior, generating electric and magnetic fields by the currents that spread through the brain tissue and have an effect on the scalp sensors. Brain areas spatially separated create large-scale dynamic networks that are described by functional and effective connectivity. The proposition is that this phenomenon behaves like a fluidic spreading, so we can use the PT, through the topological analysis we detect specific signatures related to neural phenomena that manifest changes in the behavior of synaptic diffusion. This signature must be characterized by the Fractal Dimension (FD) values of the scattering clusters, these values will be used as properties in the k-Nearest Neighbors (kNN) method, an TICA will be categorized according to the degree of similarity to the preexisting patterns. In this context, our hypothesis will consolidate as a more computational resource in the service of medicine and another way that opens with the possibility of analysis and detailed inferences of the brain through TICA that go beyond a simply visual observation, as it happens in the present day.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Eletroencefalografia/métodos , Vias Neurais/fisiologia , Análise por Conglomerados , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Cor , Difusão , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Campos Magnéticos , Modelos Neurológicos , Movimento , Doenças do Sistema Nervoso/fisiopatologia , Software , Sinapses
11.
Brain Nerve ; 71(3): 249-256, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30827958

RESUMO

Identification of various spine and spinal cord disordes using anatomical diagnosis (neurological diagnosis) and imaging diagnosis is essential for effective caring of patients with these disorders; however, sometimes, dissociation of the two diagnoses is encountered. There is a risk of a diagnosis error if the causative pathophysiology of this dissociation is not understood. To avoid this error, it is necessary to fully understand the related pathophysiology of these disorders, including deviation of spinal cord segment from the spine, central cord syndrome, sensory disturbance of cervical radiculopathy, epiconus syndrome and conus medullaris syndrome, tethered spinal cord syndrome and lumbar intraforaminal and extraforaminal nerve root disturbance.


Assuntos
Doenças do Sistema Nervoso/diagnóstico , Técnicas de Diagnóstico Neurológico , Humanos , Doenças do Sistema Nervoso/fisiopatologia
12.
J Korean Med Sci ; 34(9): e73, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30863269

RESUMO

Background: Longer transport adversely affects outcomes in out-of-hospital cardiac arrest (OHCA) patients who do not return to spontaneous circulation (ROSC). The aim of this study was to determine the association between the transport time interval (TTI) and neurological outcomes in OHCA patients without ROSC. Methods: We analyzed adult OHCA patients with presumed cardiac etiology and without prehospital ROSC from 2012 to 2015. The study population was divided into 2 groups according to STI (short STI [1-5 minutes] and long STI [≥ 6 minutes]). The primary exposure was TTI, which was categorized as short (1-5 minutes), intermediate (6-10 minutes), or long (≥ 11 minutes). The primary outcome was a good neurological recovery at discharge. Multiple logistic regression analysis was used in each STI group. Results: Among 57,822 patients, 23,043 (40%), 20,985 (36%), and 13,794 (24%) were classified as short, intermediate, and long TTI group. A good neurological recovery occurred in 1.0%, 0.6%, and 0.3% of the patients in the short, intermediate and long TTI group, respectively. Among 12,652 patients with short STI, a good neurological recovery occurred in 2.2%, 1.0%, and 0.4% of the patients in the short, intermediate and long TTI group, respectively. Among 45,570 patients with long STI, a good neurological recovery occurred in 0.7%, 0.5%, and 0.3% of the patients in the short, intermediate and long TTI group, respectively. When short TTI was used as a reference, the adjusted odds ratios (AOR) of TTI for good neurological recovery was different between short STI group and long STI group (AOR [95% confidence interval, 0.46 [0.32-0.67] vs. 0.72 [0.59-0.89], respectively, for intermediate TTI and 0.31 [0.17-0.55] vs. 0.49 [0.37-0.65], respectively, for long TTI). Conclusion: A longer TTI adversely affected the likelihood of a good neurological recovery in OHCA patients without prehospital ROSC. This negative effect was more prominent in short STI group.


Assuntos
Reanimação Cardiopulmonar , Doenças do Sistema Nervoso/fisiopatologia , Parada Cardíaca Extra-Hospitalar/terapia , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Eletrocardiografia , Serviços Médicos de Emergência , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Razão de Chances , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
14.
Trends Pharmacol Sci ; 40(4): 278-293, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30871735

RESUMO

The family of adhesion G protein-coupled receptors (aGPCRs) consists of 33 members in humans. Although the majority are orphan receptors with unknown functions, many reports have demonstrated critical functions for some members of this family in organogenesis, neurodevelopment, myelination, angiogenesis, and cancer progression. Importantly, mutations in several aGPCRs have been linked to human diseases. The crystal structure of a shared protein domain, the GPCR Autoproteolysis INducing (GAIN) domain, has enabled the discovery of a common signaling mechanism - a tethered agonist - for this class of receptors. A series of recent reports has shed new light on their biological functions and disease relevance. This review focuses on these recent advances in our understanding of aGPCR biology in the nervous system and the untapped potential of aGPCRs as novel therapeutic targets for neurological disease.


Assuntos
Terapia de Alvo Molecular , Doenças do Sistema Nervoso/tratamento farmacológico , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Desenvolvimento de Medicamentos/métodos , Humanos , Mutação , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/fisiopatologia , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais
15.
PLoS Comput Biol ; 15(3): e1006854, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30856171

RESUMO

Manipulating the dynamics of neural systems through targeted stimulation is a frontier of research and clinical neuroscience; however, the control schemes considered for neural systems are mismatched for the unique needs of manipulating neural dynamics. An appropriate control method should respect the variability in neural systems, incorporating moment to moment "input" to the neural dynamics and behaving based on the current neural state, irrespective of the past trajectory. We propose such a controller under a nonlinear state-space feedback framework that steers one dynamical system to function as through it were another dynamical system entirely. This "myopic" controller is formulated through a novel variant of a model reference control cost that manipulates dynamics in a short-sighted manner that only sets a target trajectory of a single time step into the future (hence its myopic nature), which omits the need to pre-calculate a rigid and computationally costly neural feedback control solution. To demonstrate the breadth of this control's utility, two examples with distinctly different applications in neuroscience are studied. First, we show the myopic control's utility to probe the causal link between dynamics and behavior for cognitive processes by transforming a winner-take-all decision-making system to operate as a robust neural integrator of evidence. Second, an unhealthy motor-like system containing an unwanted beta-oscillation spiral attractor is controlled to function as a healthy motor system, a relevant clinical example for neurological disorders.


Assuntos
Redes Neurais (Computação) , Algoritmos , Tomada de Decisões , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Dinâmica não Linear
16.
Life Sci ; 221: 130-134, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30769113

RESUMO

Autophagy is a conservative catabolism process, participating in delivering the cytosol and cytosolic components to the lysosome. Abnormal autophagy is related to human pathologies, for instance diabetes, neurodegeneration, cardiovascular, macular degeneration, pulmonary, and cancer. Enormous evidences indicate that autophagy may mediate the cellular pathological condition in the process of neurological diseases. Exercise as a form of physiological stress may cause an adaptation, and autophagy is a necessary process for adaptational response to exercise. Autophagy during exercise may improve neurological function, control tissue maintain tissue integrity, and activate different signals pathway for adaptation. In this review, we summarize the possible mechanisms of exercise training via autophagy in neurological diseases.


Assuntos
Autofagia/fisiologia , Exercício/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Aclimatação , Adaptação Fisiológica , Animais , Humanos , Lisossomos , Modelos Biológicos , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Transdução de Sinais , Estresse Fisiológico
17.
Int J Dev Neurosci ; 74: 11-17, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30763607

RESUMO

DAPK (death-associated protein kinase) is a calcium/calmodulin (Ca2+/CaM) regulated serine/threonine kinase. Structurally, it assumes a multi-domain structure and participates in various apoptotic systems which imply that it may interact with a wide range of intracellular components to exert its action. DAPK plays vital roles in pro-apoptotic, apoptotic and autophagic pathways. In addition, it plays important roles in many diseases such as cancer, Alzheimer's disease, cerebral ischemia and epilepsy. Although a novel protein, DAPK's various cellular signal transduction pathways proves that it can be a target for a potential future therapeutic effects. Specific role of DAPK in the development and maintenance of the nervous system needs to be further investigated as it is involved in neurodegeneration, traumatic brain injury and neuronal development or recovery from injury. This review summarizes DAPK signaling pathways in autophagy, apoptosis, and stresses the important role it might play in the nervous system.


Assuntos
Autofagia/fisiologia , Proteínas Quinases Associadas com Morte Celular/metabolismo , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/fisiologia , Humanos
18.
Gait Posture ; 70: 33-38, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30802642

RESUMO

BACKGROUND: The timed up and go (TUG) test is widely used for assessing treatments effectiveness on elderly mobility. Although the TUG test consists of different tasks (e.g. walking and turning), the total TUG duration (TTD) is usually the only outcome measure, with TTD shortening indicating the patient's improvement. RESEARCH QUESTION: Does TTD shortening reflect the improvement of each TUG tasks or does it reflect the improvement of only some of them? METHODS: This retrospective study recruited 120 elderly patients (mean, SD: 76.9, 6.6 years) admitted to inpatient rehabilitation because of an acute or chronic neurological disease (acute patients, AP; chronic patients, CP). TTD and TUG tasks duration was measured on admission and discharge (five trials/session) by means of the instrumental TUG test (ITUG). Likelihood ratios (LRs) were used for inferring TUG tasks improvement from TTD improvement. TTD and TUG tasks have improved if at least four measurements on discharge were shorter than the shortest measurement on admission. RESULTS: TTD improvement per se is not enough to claim that all the TUG tasks have improved (LR+AP = 1.32; LR+CP = 1.85). Conversely, if TTD has not improved, not even a single TUG task has improved (LR-AP = 0.13; LR-CP = 0.19). If TTD has improved, there is at least one TUG task that actually improved (LR+AP = 3.17; LR+CP = 9.54). The improvement of all TUG tasks can be only inferred in the (unusual) event of a large TTD shortening (AP: >39%, LR+AP = 6.26; CP: >30%, LR+CP = 9.0). SIGNIFICANCE: In most cases, TTD improvement is not associated with the improvement of all TUG tasks. Moreover, when TTD has improved there is at least a TUG task that has improved, but that remains unknown. To actually understand how treatments ameliorate patients' mobility, ITUG with TUG task duration measurement should be preferred to TTD.


Assuntos
Teste de Esforço/métodos , Doenças do Sistema Nervoso/reabilitação , Caminhada/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doenças do Sistema Nervoso/fisiopatologia , Equilíbrio Postural , Estudos Retrospectivos , Estudos de Tempo e Movimento
19.
Artigo em Inglês | MEDLINE | ID: mdl-30654089

RESUMO

Dendritic spines are small, thin, specialized protrusions from neuronal dendrites, primarily localized in the excitatory synapses. Sophisticated imaging techniques revealed that dendritic spines are complex structures consisting of a dense network of cytoskeletal, transmembrane and scaffolding molecules, and numerous surface receptors. Molecular signaling pathways, mainly Rho and Ras family small GTPases pathways that converge on actin cytoskeleton, regulate the spine morphology and dynamics bi-directionally during synaptic activity. During synaptic plasticity the number and shapes of dendritic spines undergo radical reorganizations. Long-term potentiation (LTP) induction promote spine head enlargement and the formation and stabilization of new spines. Long-term depression (LTD) results in their shrinkage and retraction. Reports indicate increased spine density in the pyramidal neurons of autism and Fragile X syndrome patients and reduced density in the temporal gyrus loci of schizophrenic patients. Post-mortem reports of Alzheimer's brains showed reduced spine number in the hippocampus and cortex. This review highlights the spine morphogenesis process, the activity-dependent structural plasticity and mechanisms by which synaptic activity sculpts the dendritic spines, the structural and functional changes in spines during learning and memory using LTP and LTD processes. It also discusses on spine status in neurodegenerative diseases and the impact of nootropics and neuroprotective agents on the functional restoration of dendritic spines.


Assuntos
Espinhas Dendríticas/fisiologia , Animais , Espinhas Dendríticas/efeitos dos fármacos , Humanos , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Plasticidade Neuronal/fisiologia
20.
Lipids Health Dis ; 18(1): 26, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683111

RESUMO

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.


Assuntos
Encéfalo/crescimento & desenvolvimento , Colesterol/metabolismo , Doenças do Sistema Nervoso/genética , Esfingolipídeos/metabolismo , Animais , Encéfalo/metabolismo , Membrana Celular/genética , Colesterol/genética , Humanos , Lipídeos/genética , Microdomínios da Membrana/genética , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Esfingolipídeos/genética
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