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Pesquisa : G07.568.500 [Categoria DeCS]
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  1 / 21741 MEDLINE  
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[PMID]:29346425
[Au] Autor:Hooper A; Fuller PM; Maguire J
[Ad] Endereço:Tufts University School of Medicine, Department of Neuroscience, Boston, Massachusetts.
[Ti] Título:Hippocampal corticotropin-releasing hormone neurons support recognition memory and modulate hippocampal excitability.
[So] Source:PLoS One;13(1):e0191363, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corticotropin-releasing hormone (CRH) signaling in the hippocampus has been established to be important for mediating the effects of stress on learning and memory. Given our laboratory's recent characterization of a subset of hippocampal CRH neurons as a novel class of GABAergic interneurons, we hypothesized that these local GABAergic hippocampal CRH neurons may influence hippocampal function. Here we applied an array of molecular tools to selectively label and manipulate hippocampal CRH neurons in mice, in order to assess this interneuron population's impact on hippocampus-dependent behaviors and hippocampal network excitability. Genetically-targeted ablation of hippocampal CRH neurons in vivo impaired object recognition memory and substantially enhanced the severity of kainic acid-induced seizures. Conversely, selective activation of CRH neurons in vitro suppressed the excitability of the mossy fiber-CA3 pathway. Additional experiments are needed to reconcile the functions of GABA and CRH signaling of hippocampal CRH neurons on hippocampal function. However, our results indicate that this interneuron population plays an important role in maintaining adaptive network excitability, and provide a specific circuit-level mechanism for this role.
[Mh] Termos MeSH primário: Região CA3 Hipocampal/metabolismo
Hormônio Liberador da Corticotropina/metabolismo
Neurônios GABAérgicos/metabolismo
Memória
[Mh] Termos MeSH secundário: Animais
Região CA3 Hipocampal/citologia
Eletroencefalografia
Locomoção
Camundongos
Camundongos Transgênicos
Técnicas de Patch-Clamp
Transdução de Sinais
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
56-12-2 (gamma-Aminobutyric Acid); 9015-71-8 (Corticotropin-Releasing Hormone)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191363


  2 / 21741 MEDLINE  
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[PMID]:28456012
[Au] Autor:Alizadeh A; Dyck SM; Kataria H; Shahriary GM; Nguyen DH; Santhosh KT; Karimi-Abdolrezaee S
[Ad] Endereço:Regenerative Medicine Program, Department of Physiology and Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
[Ti] Título:Neuregulin-1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury.
[So] Source:Glia;65(7):1152-1175, 2017 Jul.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically-relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg-1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin-10 and arginase-1 expression. We also found a decrease in proinflammatory factors including IL-1ß, TNF-α, matrix metalloproteinases (MMP-2 and 9) and nitric oxide after injury. In addition, Nrg-1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg-1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg-1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll-like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg-1 treatment with the therapeutic dosage of 1.5 µg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg-1 in acute SCI and suggest a positive immunomodulatory role for Nrg-1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso/tratamento farmacológico
Doenças do Sistema Nervoso/etiologia
Neuregulina-1/uso terapêutico
Neuroglia/fisiologia
Recuperação de Função Fisiológica/fisiologia
Traumatismos da Medula Espinal/complicações
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Arginase/metabolismo
Células Cultivadas
Meios de Cultivo Condicionados/farmacologia
Modelos Animais de Doenças
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/fisiologia
Proteína Glial Fibrilar Ácida/metabolismo
Interleucina-10/metabolismo
Lipopolissacarídeos/toxicidade
Locomoção/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Neuregulina-1/metabolismo
Neuregulina-1/farmacologia
Neuroglia/efeitos dos fármacos
Ratos
Recuperação de Função Fisiológica/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Traumatismos da Medula Espinal/patologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media, Conditioned); 0 (Glial Fibrillary Acidic Protein); 0 (Lipopolysaccharides); 0 (Neuregulin-1); 130068-27-8 (Interleukin-10); EC 3.5.3.1 (Arginase); EC 3.5.3.1 (arginase I, rat)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23150


  3 / 21741 MEDLINE  
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[PMID]:28747460
[Au] Autor:Schallner N; Lieberum JL; Gallo D; LeBlanc RH; Fuller PM; Hanafy KA; Otterbein LE
[Ad] Endereço:From the Department of Surgery (N.S., J.-L.L., D.G., L.E.O.) and Department of Neurology (R.H.L., P.M.F., K.A.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Anesthesiology and Critical Care, Medical Center-University Freiburg, Faculty of Medicine, German
[Ti] Título:Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice.
[So] Source:Stroke;48(9):2565-2573, 2017 09.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is associated with a temporal pattern of stroke incidence. We hypothesized that natural oscillations in gene expression controlling circadian rhythm affect the severity of neuronal injury. We moreover predict that heme oxygenase-1 (HO-1/ ) and its product carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection. METHODS: Murine SAH model was used where blood was injected at various time points of the circadian cycle. Readouts included circadian clock gene expression, locomotor activity, vasospasm, neuroinflammatory markers, and apoptosis. In addition, cerebrospinal fluid and peripheral blood leukocytes from SAH patients and controls were analyzed for clock gene expression. RESULTS: Significant elevations in the clock genes , , and were observed in the hippocampus, cortex, and suprachiasmatic nucleus in mice subjected to SAH at zeitgeber time (ZT) 12 when compared with ZT2. Clock gene expression amplitude correlated with basal expression of HO-1, which was also significantly greater at ZT12. SAH animals showed a significant reduction in cerebral vasospasm, neuronal apoptosis, and microglial activation at ZT12 compared with ZT2. In animals with myeloid-specific HO-1 deletion ( ), , and expression was reduced in the suprachiasmatic nucleus, which correlated with increased injury. Treatment with low-dose CO rescued mice, restored , expression, and reduced neuronal apoptosis. CONCLUSIONS: Clock gene expression regulates, in part, the severity of SAH and requires myeloid HO-1 activity to clear the erythrocyte burden and inhibit neuronal apoptosis. Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH.
[Mh] Termos MeSH primário: Monóxido de Carbono/metabolismo
Ritmo Circadiano/genética
Expressão Gênica/efeitos dos fármacos
Heme Oxigenase-1/genética
Proteínas de Membrana/genética
Hemorragia Subaracnóidea/genética
[Mh] Termos MeSH secundário: Fatores de Transcrição ARNTL/genética
Animais
Apoptose
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Proteínas CLOCK/genética
Líquido Cefalorraquidiano/metabolismo
Heme Oxigenase-1/metabolismo
Seres Humanos
Imuno-Histoquímica
Inflamação
Leucócitos/metabolismo
Locomoção
Proteínas de Membrana/metabolismo
Camundongos
Proteínas do Tecido Nervoso/genética
Proteínas Circadianas Period/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Índice de Gravidade de Doença
Núcleo Supraquiasmático/metabolismo
Vasoespasmo Intracraniano
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ARNTL Transcription Factors); 0 (Arntl protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Npas2 protein, mouse); 0 (PER2 protein, human); 0 (Per1 protein, mouse); 0 (Per2 protein, mouse); 0 (Period Circadian Proteins); 7U1EE4V452 (Carbon Monoxide); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.14.18 (Hmox1 protein, mouse); EC 2.3.1.48 (CLOCK Proteins); EC 2.3.1.48 (Clock protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.116.016165


  4 / 21741 MEDLINE  
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[PMID]:28747158
[Au] Autor:Iwaya T; Doi T; Seichi A; Hoshino Y; Ogata T; Akai M
[Ad] Endereço:Nagano University of Health and Medicine, 11-1 Imaihara Kawanajima-chou Nagano-shi, Nagano, 381-2227, Japan.
[Ti] Título:Characteristics of disability in activity of daily living in elderly people associated with locomotive disorders.
[So] Source:BMC Geriatr;17(1):165, 2017 Jul 26.
[Is] ISSN:1471-2318
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ageing is associated with a decline of motor function and ability to perform daily activities. Locomotive disorders are one of the major disorders resulting in adverse health condition in elderly people. Concept of Locomotive syndrome (LoS) was proposed to tackle the problems and prolong healthy life expectancy of people with locomotive disorders. To develop intervention strategy for LoS it is mandatory to investigate impairments, functional disabilities which people with locomotive disorder experience and to examine relationships among these parameters. For this purpose we have developed Geriatric Locomotive Function Scale-25 (GLFS-25). Though several physical performance tests were reported for identification or monitoring the severity of LoS, there are few studies reported on characteristics of disability which people with locomotive disorders experience. The aim of this study was to report the characteristics of ADL disabilities in elderly people with locomotive disorders in terms of numbers and degree of activity limitations. METHODS: We organized a cohort study and recruited 314 participants aged 65 years and over from five orthopedic clinics or nursing care facilities. This was a cross-sectional study to use the baseline data of such cohort. ADL disabilities were assessed using GLFS-25 scale arranging the GLFS-25 scores in ordinal levels using "R language" program. Numbers and degrees of activity limitations were determined and compared among the levels. Frequency of limitation in activities regarding social activity, housework, locomotion, mobility and self-care was compared among across the disability level. RESULTS: The GLFS-25 score was mathematically categorized into 7 levels. The number of activity limitations and the degrees of each activity limitation were significantly greater in high GLFS-25 levels than in low levels. Difficulties in mobility appeared in less severe level, difficulties in domestic and social life appeared in moderately severe level, and difficulties in self-care appeared in advanced level. CONCLUSIONS: High GLFS-25 score represented high degree of disability on ADLs. Concordant increase of numbers of activity limitation and severity progression in activity limitation may contribute to progression of disability. Activity limitation may occur in the following order: sports activity, walking, transferring, and self-care.
[Mh] Termos MeSH primário: Atividades Cotidianas
Avaliação da Deficiência
Avaliação Geriátrica
Locomoção
Limitação da Mobilidade
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Estudos de Coortes
Estudos Transversais
Feminino
Seres Humanos
Masculino
Meia-Idade
Qualidade de Vida
Autocuidado
Síndrome
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1186/s12877-017-0543-z


  5 / 21741 MEDLINE  
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[PMID]:29380887
[Au] Autor:Young JW; Shapiro LJ
[Ad] Endereço:Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio, 44272.
[Ti] Título:Developments in development: What have we learned from primate locomotor ontogeny?
[So] Source:Am J Phys Anthropol;165 Suppl 65:37-71, 2018 01.
[Is] ISSN:1096-8644
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The importance of locomotion to evolutionary fitness has led to extensive study of primate locomotor behavior, morphology and ecology. Most previous research has focused on adult primates, but in the last few decades, increased attention to locomotor development has provided new insights toward our broader understanding of primate adaptation and evolution. Here, we review the contributions of this body of work from three basic perspectives. First, we assess possible determinants on the timing of locomotor independence, an important life history event. Significant influences on timing of locomotor independence include adult female body mass, age at weaning, and especially relative brain size, a significant predictor of other primate life history variables. Additionally, we found significant phylogenetic differences in the timing of locomotor independence, even accounting for these influences. Second, we discuss how structural aspects of primate growth may enhance the locomotor performance and safety of young primates, despite their inherent neuromotor and musculoskeletal limitations. For example, compared to adults, growing primates have greater muscle mechanical advantage, greater bone robusticity, and larger extremities with relatively long digits. Third, focusing on primate quadrupedalism, we provide examples that illustrate how ontogenetic transitions in morphology and locomotion can serve as a model system for testing broader principles underlying primate locomotor biomechanics. This approach has led to a better understanding of the key features that contribute to primates' stride characteristics, gait patterns, limb force distribution, and limb postures. We have learned a great deal from the study of locomotor ontogeny, but there is much left to explore. We conclude by offering guidelines for future research, both in the laboratory and the field.
[Mh] Termos MeSH primário: Fenômenos Biomecânicos/fisiologia
Marcha/fisiologia
Locomoção/fisiologia
Primatas/fisiologia
[Mh] Termos MeSH secundário: Animais
Antropologia Física
Osso e Ossos/fisiologia
Feminino
Força da Mão/fisiologia
Seres Humanos
Masculino
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1002/ajpa.23388


  6 / 21741 MEDLINE  
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[PMID]:29324345
[Au] Autor:Xu M; Wang Y; Yang F; Wu C; Wang Z; Ye B; Jiang X; Zhao Q; Li J; Liu Y; Zhang J; Tian G; He Y; Shen J; Jiang H
[Ad] Endereço:CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
[Ti] Título:Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect.
[So] Source:Eur J Med Chem;145:74-85, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D , serotonin 5-HT and 5-HT receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D /5-HT /5-HT receptors, but also endowed with low to moderate activities on 5-HT , H , α , M receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In animal behavioral studies, 3d reduced phencyclidine-induced hyperlocomotion with a high threshold for catalepsy induction. Compound 3d was selected as a potential antipsychotic candidate for further development.
[Mh] Termos MeSH primário: Antipsicóticos/farmacologia
Catalepsia/tratamento farmacológico
Imidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/síntese química
Antipsicóticos/química
Catalepsia/induzido quimicamente
Relação Dose-Resposta a Droga
Seres Humanos
Imidas/síntese química
Imidas/química
Locomoção/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos ICR
Estrutura Molecular
Fenciclidina
Ratos
Ratos Sprague-Dawley
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Imides); J1DOI7UV76 (Phencyclidine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


  7 / 21741 MEDLINE  
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[PMID]:29281635
[Au] Autor:Takahashi M; Takagi S
[Ad] Endereço:Division of Biological Science, Nagoya University Graduate School of Science Chikusa-ku, Nagoya, Japan.
[Ti] Título:Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans.
[So] Source:PLoS Genet;13(12):e1007134, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination. Pumping was similarly inhibited by illumination in locomotion-defective mutants carrying Arch, suggesting that perturbation of locomotory movement is not critical for pumping inhibition. Analysis of mutants and cell ablation experiments showed that the signals mediating the pumping inhibition response triggered by activation of Arch with weak light are transferred mainly through two pathways: one involving gap junction-dependent mechanisms through pharyngeal I1 neurons, which mediate fast signals, and the other involving dense-core vesicle-dependent mechanisms, which mediate slow signals. Activation of Arch with strong light inhibited pumping strongly in a manner that does not rely on either gap junction-dependent or dense-core vesicle-dependent mechanisms. Our study revealed a new aspect of the neural and neuroendocrine controls of pumping initiated from the body wall muscles.
[Mh] Termos MeSH primário: Optogenética/métodos
Músculos Faríngeos/metabolismo
Bombas de Próton/metabolismo
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans
Proteínas de Caenorhabditis elegans/metabolismo
Ingestão de Alimentos/fisiologia
Locomoção/fisiologia
Neurônios Motores/metabolismo
Músculo Esquelético/metabolismo
Faringe/metabolismo
Serotonina
Transdução de Sinais/fisiologia
Canais de Ânion Dependentes de Voltagem/genética
Canais de Ânion Dependentes de Voltagem/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Proton Pumps); 0 (Voltage-Dependent Anion Channels); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007134


  8 / 21741 MEDLINE  
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[PMID]:28457669
[Au] Autor:Kamens HM; Peck C; Garrity C; Gechlik A; Jenkins BC; Rajan A
[Ad] Endereço:Department of Biobehavioral Health, Penn State University, University Park, PA, USA; Center for Brain, Behavior, and Cognition, Penn State University, University Park, PA, USA. Electronic address: hmk123@psu.edu.
[Ti] Título:α6ß2 nicotinic acetylcholine receptors influence locomotor activity and ethanol consumption.
[So] Source:Alcohol;61:43-49, 2017 Jun.
[Is] ISSN:1873-6823
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6ß2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach. The aim of this study was to examine the role of α6ß2 nAChRs in ethanol behaviors using a pharmacological approach. Adolescent C57BL/6J mice were treated with bPiDI 30 min prior to testing the mice for binge-like ethanol consumption in the drinking-in-the-dark (DID) test, ethanol-induced motor incoordination using the balance beam, and ethanol-induced sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals were chosen because they express a high amount of α6 mRNA relative to adult animals. Control studies were also performed to determine the effect of bPiDI on locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg bPiDI had reduced locomotor activity compared to saline-treated animals during the first 30 min following an acute injection. Pretreatment with the α6ß2 antagonist reduced adolescent ethanol consumption but also reduced saccharin consumption. No significant effects were observed on ethanol-induced ataxia, sedation, or metabolism. This study provides evidence that α6ß2 nAChRs are involved in locomotor activity as well as ethanol and saccharin consumption in adolescent animals.
[Mh] Termos MeSH primário: Consumo de Bebidas Alcoólicas/fisiopatologia
Etanol/administração & dosagem
Locomoção/efeitos dos fármacos
Receptores Nicotínicos/fisiologia
[Mh] Termos MeSH secundário: Consumo de Bebidas Alcoólicas/prevenção & controle
Animais
Bebedeira/fisiopatologia
Etanol/efeitos adversos
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Antagonistas Nicotínicos/farmacologia
Picolinas/farmacologia
Compostos de Piridínio/farmacologia
Sacarina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N,N-decane-1,10-diyl-bis-3-picolinium); 0 (Nicotinic Antagonists); 0 (Picolines); 0 (Pyridinium Compounds); 0 (Receptors, Nicotinic); 0 (alpha6beta2 nicotinic acetylcholine receptor); 3K9958V90M (Ethanol); FST467XS7D (Saccharin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  9 / 21741 MEDLINE  
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[PMID]:28451641
[Au] Autor:Yu J; Yang W; Liu H; Hao Y; Zhang Y
[Ad] Endereço:Department of Organismic and Evolutionary Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138.
[Ti] Título:An Aversive Response to Osmotic Upshift in .
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Environmental osmolarity presents a common type of sensory stimulus to animals. While behavioral responses to osmotic changes are important for maintaining a stable intracellular osmolarity, the underlying mechanisms are not fully understood. In the natural habitat of , changes in environmental osmolarity are commonplace. It is known that the nematode acutely avoids shocks of extremely high osmolarity. Here, we show that also generates gradually increased aversion of mild upshifts in environmental osmolarity. Different from an acute avoidance of osmotic shocks that depends on the function of a transient receptor potential vanilloid channel, the slow aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX-2. TAX-2 acts in several sensory neurons that are exposed to body fluid to generate the aversive response through a motor network that underlies navigation. Osmotic upshifts activate the body cavity sensory neuron URX, which is known to induce aversion upon activation. Together, our results characterize the molecular and cellular mechanisms underlying a novel sensorimotor response to osmotic stimuli and reveal that engages different behaviors and the underlying mechanisms to regulate responses to extracellular osmolarity.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Canais Iônicos/metabolismo
Osmorregulação
Células Receptoras Sensoriais/metabolismo
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans
Locomoção
Pressão Osmótica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Ion Channels); 0 (tax-2 protein, C elegans)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29385166
[Au] Autor:Hubscher CH; Herrity AN; Williams CS; Montgomery LR; Willhite AM; Angeli CA; Harkema SJ
[Ad] Endereço:Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky, United States of America.
[Ti] Título:Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.
[So] Source:PLoS One;13(1):e0190998, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). STUDY DESIGN: Prospective cohort study; pilot trial with small sample size. METHODS: Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. RESULTS: Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. CONCLUSIONS: These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03036527.
[Mh] Termos MeSH primário: Colo/fisiopatologia
Locomoção
Sexualidade
Traumatismos da Medula Espinal/reabilitação
Bexiga Urinária/fisiopatologia
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Estudos Prospectivos
Recuperação de Função Fisiológica
Traumatismos da Medula Espinal/fisiopatologia
Inquéritos e Questionários
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190998



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