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  1 / 18006 MEDLINE  
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[PMID]:28466071
[Au] Autor:Walton JC; McNeill JK; Oliver KA; Albers HE
[Ad] Endereço:Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
[Ti] Título:Temporal Regulation of GABA Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus.
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent molecular studies suggest that the expression levels of δ and γ2 GABA receptor (GABA R) subunits regulate the balance between synaptic and extrasynaptic GABA neurotransmission in multiple brain regions. We investigated the expression of GABA δ and GABA γ2 and the functional significance of a change in balance between these subunits in a robust local GABA network contained within the suprachiasmatic nucleus of the hypothalamus (SCN). Muscimol, which can activate both synaptic and extrasynaptic GABA Rs, injected into the SCN during the day phase advanced the circadian pacemaker, whereas injection of the extrasynaptic GABA superagonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) had no effect on circadian phase. In contrast, injection of either THIP or muscimol during the night was sufficient to block the phase shifting effects of light. Gene expression analysis of the whole SCN revealed different temporal patterns in GABA δ and GABA γ2 mRNA expression. When examined across all subregions of the SCN, quantitative immunohistochemical analysis found no significant variations in GABA δ protein immunoreactivity (IR) but did find significant variations in GABA γ2 protein-IR in hamsters housed in either LD cycles or in constant darkness. Remarkably, significant interactions in the ratio of GABA δ:GABA γ2 subunits between lighting condition and circadian phase occurred only within one highly discrete anatomical area of the SCN; a region that functions as the input for lighting information from the retina. Taken together, these data support the hypothesis that the balance between synaptic and extrasynaptic GABA Rs determines the functional response to GABA, and that this balance is differentially regulated in a region-specific manner.
[Mh] Termos MeSH primário: Receptores de GABA-A/metabolismo
Núcleo Supraquiasmático/metabolismo
[Mh] Termos MeSH secundário: Animais
Ritmo Circadiano/efeitos dos fármacos
Ritmo Circadiano/fisiologia
Agonistas GABAérgicos/farmacologia
Masculino
Receptores de GABA-A/efeitos dos fármacos
Núcleo Supraquiasmático/efeitos dos fármacos
Sinapses/efeitos dos fármacos
Sinapses/metabolismo
Transmissão Sináptica/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA Agonists); 0 (Receptors, GABA-A)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  2 / 18006 MEDLINE  
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[PMID]:29390378
[Au] Autor:Zhang Y; Lian Y; Xie N
[Ad] Endereço:Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
[Ti] Título:Early onset epileptic encephalopathy with a novel GABRB3 mutation treated effectively with clonazepam: A case report.
[So] Source:Medicine (Baltimore);96(50):e9273, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Early onset epileptic encephalopathy (EOEE) is one of the most serious early onset epilepsies. The etiopathology of this condition remains unclear, and recent evidence indicated that gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 (GABRB3) gene mutations might be associated with EOEE. Furthermore, the therapeutic regimen for EOEE has yet to be well elucidated. Herein, we reported the clinical and genetic features of a case with GABRB3-related EOEE. PATIENT CONCERNS: A 6-year-old girl developed epileptic seizures 3 days after birth. She presented with multiple seizure types including myoclonic seizures, spasms, and absence seizures. Serial electroencephalographic examinations showed variable abnormalities, and intellectual evaluation revealed significant development retardation. Conventional antiepileptic drugs were ineffective for the seizure controlling. Genetic screening identified a novel nonsense mutation (C.5G > A, p.W2X) in the GABRB3 gene. DIAGNOSES: Early onset epileptic encephalopathy. INTERVENTIONS: We changed the antiepileptic strategy to oral clonazepam (0.5mg twice daily). The patient was followed up once a week and significant declining in the attack frequency was noted 1 week later (2-3 times daily). Subsequently, the dosage was doubled (1mg twice daily), and complete cessation of seizures was achieved 20 days later. OUTCOMES: Through a 9-month follow up,the girl remained seizure-free. LESSONS: This study identified a novel nonsensemutation (C.5G>A) in the exon 1 of GABRB3 Gene, which may be associated with EOEE. To our knowledge, this is the first report to use clonazepam in the patient with GABRB3-related EOEE with favorable outcome. Our finding suggested that clonazepam might be a choice for patient with GABRB3-related EOEE. The remarkable efficacy of clonazepam in the control of seizures indicated a potential GABRB3- or GABA-related mechanism involved in the development of EOEE.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Clonazepam/uso terapêutico
Epilepsia/tratamento farmacológico
Epilepsia/genética
Receptores de GABA-A/genética
[Mh] Termos MeSH secundário: Idade de Início
Criança
Códon sem Sentido
Análise Mutacional de DNA
Deficiências do Desenvolvimento
Eletroencefalografia
Feminino
Predisposição Genética para Doença
Testes Genéticos
Seres Humanos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Codon, Nonsense); 0 (GABRB3 protein, human); 0 (Receptors, GABA-A); 5PE9FDE8GB (Clonazepam)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009273


  3 / 18006 MEDLINE  
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[PMID]:28452419
[Au] Autor:Joshi S; Rajasekaran K; Williamson J; Kapur J
[Ad] Endereço:Department of Neurology, University of Virginia, Charlottesville, Virginia, U.S.A.
[Ti] Título:Neurosteroid-sensitive δ-GABA receptors: A role in epileptogenesis?
[So] Source:Epilepsia;58(3):494-504, 2017 03.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We determined the role of the neurosteroid-sensitive δ subunit-containing γ-aminobutyric acid A receptors (δ-GABARs) in epileptogenesis. METHODS: Status epilepticus (SE) was induced via lithium pilocarpine in adult rats, and seizures were assessed by continuous video-electroencephalography (EEG) monitoring. Finasteride was administered to inhibit neurosteroid synthesis. The total and surface protein expression of hippocampal δ, α4, and γ2 GABAR subunits was studied using biotinylation assays and Western blotting. Neurosteroid potentiation of the tonic currents of dentate granule cells (DGCs) was measured by whole-cell patch-clamp technique. Finally, the effects of inhibiting N-methyl-d-aspartate receptors (NMDARs) during SE on the long-term plasticity of δ-GABARs, neurosteroid-induced modulation of tonic current, and epileptogenesis were studied. RESULTS: The inhibition of neurosteroid synthesis 4 days after SE triggered acute seizures and accelerated the onset of chronic recurrent spontaneous seizures (epilepsy). The down-regulation of neurosteroid-sensitive δ-GABARs occurred prior to the onset of epilepsy, whereas an increased expression of the γ2-GABAR subunits occurred after seizure onset. MK801 blockade of NMDARs during SE preserved the expression of neurosteroid-sensitive δ-GABARs. NMDAR blockade during SE also prevented the onset of spontaneous seizures. SIGNIFICANCE: Changes in neurosteroid-sensitive δ-GABAR expression correlated temporally with epileptogenesis. These findings raise the possibility that δ-GABAR plasticity may play a role in epileptogenesis.
[Mh] Termos MeSH primário: Epilepsia do Lobo Temporal/fisiopatologia
Neurotransmissores/fisiologia
Receptores de GABA-A/fisiologia
Estado Epiléptico/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Giro Denteado/fisiopatologia
Modelos Animais de Doenças
Maleato de Dizocilpina/farmacologia
Regulação para Baixo/efeitos dos fármacos
Regulação para Baixo/fisiologia
Eletroencefalografia/efeitos dos fármacos
Feminino
Finasterida/farmacologia
Hipocampo/fisiopatologia
Compostos de Lítio
Masculino
Plasticidade Neuronal/efeitos dos fármacos
Plasticidade Neuronal/fisiologia
Neurônios/efeitos dos fármacos
Neurônios/fisiologia
Neurotransmissores/antagonistas & inibidores
Técnicas de Patch-Clamp
Pilocarpina
Ratos
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
Gravação em Vídeo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lithium Compounds); 0 (Neurotransmitter Agents); 0 (Receptors, GABA-A); 0 (Receptors, N-Methyl-D-Aspartate); 01MI4Q9DI3 (Pilocarpine); 57GNO57U7G (Finasteride); 6LR8C1B66Q (Dizocilpine Maleate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13660


  4 / 18006 MEDLINE  
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[PMID]:29352320
[Au] Autor:Zhou X; Desai R; Zhang Y; Stec WJ; Miller KW; Jounaidi Y
[Ad] Endereço:Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:High-level production and purification in a functional state of an extrasynaptic gamma-aminobutyric acid type A receptor containing α4ß3δ subunits.
[So] Source:PLoS One;13(1):e0191583, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, ß- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and ß-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αßδ GABAARs remains unresolved by electrophysiological and pharmacological research. To resolve such issues will require biophysical techniques that demand quantities of receptor that have been previously unavailable. Therefore, we have engineered a stable cell line with tetracycline inducible expression of human α4-, ß3- and N-terminally Flag-tagged δ-subunits. This cell line achieved a specific activity between 15 and 20 pmol [3H]muscimol sites/mg of membrane protein, making it possible to obtain 1 nmole of purified α4ß3δ GABAAR from sixty 15-cm culture dishes. When induced, these cells exhibited agonist-induced currents with characteristics comparable to those previously reported for this receptor and a pharmacology that included strong modulation by etomidate and the δ-subunit-specific ligand, DS2. Immunoaffinity purification and reconstitution in CHAPS/asolectin micelles resulted in the retention of equilibrium allosteric interactions between the separate agonist, anesthetic and DS2 sites. Moreover, all three subunits retained glycosylation. The establishment of this well-characterized cell line will allow molecular level studies of tonic receptors to be undertaken.
[Mh] Termos MeSH primário: Receptores de GABA-A/biossíntese
[Mh] Termos MeSH secundário: Fenômenos Eletrofisiológicos
Células HEK293
Seres Humanos
Cinética
Engenharia de Proteínas
Subunidades Proteicas
Ensaio Radioligante
Receptores de GABA-A/genética
Receptores de GABA-A/isolamento & purificação
Proteínas Recombinantes de Fusão/biossíntese
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/isolamento & purificação
Transfecção
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protein Subunits); 0 (Receptors, GABA-A); 0 (Recombinant Fusion Proteins); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191583


  5 / 18006 MEDLINE  
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[PMID]:29227934
[Au] Autor:Zabela V; Hettich T; Schlotterbeck G; Wimmer L; Mihovilovic MD; Guillet F; Bouaita B; Shevchenko B; Hamburger M; Oufir M
[Ad] Endereço:Pharmaceutical Biology Laboratory, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: volha.zabela@unibas.ch.
[Ti] Título:GABA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:379-389, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In a screening of natural products for allosteric modulators of GABA receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds.
[Mh] Termos MeSH primário: Alcaloides
Benzodioxóis
Inibidores das Enzimas do Citocromo P-450
Sistema Enzimático do Citocromo P-450
Piperidinas
Alcamidas Poli-Insaturadas
Receptores de GABA-A/metabolismo
[Mh] Termos MeSH secundário: Alcaloides/análise
Alcaloides/química
Alcaloides/metabolismo
Benzodioxóis/análise
Benzodioxóis/química
Benzodioxóis/metabolismo
Cromatografia Líquida de Alta Pressão
Inibidores das Enzimas do Citocromo P-450/análise
Inibidores das Enzimas do Citocromo P-450/química
Inibidores das Enzimas do Citocromo P-450/metabolismo
Sistema Enzimático do Citocromo P-450/análise
Sistema Enzimático do Citocromo P-450/classificação
Sistema Enzimático do Citocromo P-450/metabolismo
Seres Humanos
Microssomos Hepáticos/metabolismo
Piperidinas/análise
Piperidinas/química
Piperidinas/metabolismo
Alcamidas Poli-Insaturadas/análise
Alcamidas Poli-Insaturadas/química
Alcamidas Poli-Insaturadas/metabolismo
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Benzodioxoles); 0 (Cytochrome P-450 Enzyme Inhibitors); 0 (Piperidines); 0 (Polyunsaturated Alkamides); 0 (Receptors, GABA-A); 9035-51-2 (Cytochrome P-450 Enzyme System); U71XL721QK (piperine)
[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:171212
[St] Status:MEDLINE


  6 / 18006 MEDLINE  
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[PMID]:29223589
[Au] Autor:Blanco MJ; La D; Coughlin Q; Newman CA; Griffin AM; Harrison BL; Salituro FG
[Ad] Endereço:Sage Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA. Electronic address: Maria-Jesus.Blanco@sagerx.com.
[Ti] Título:Breakthroughs in neuroactive steroid drug discovery.
[So] Source:Bioorg Med Chem Lett;28(2):61-70, 2018 01 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are effective modulators of multiple signaling pathways including receptors for the γ-aminobutyric acid A (GABA ) and glutamate, in particular N-methyl-d-aspartate (NMDA). These receptors are the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS), and there is growing evidence suggesting that dysregulation of neurosteroid production plays a role in numerous neurological disorders. The significant unmet medical need for treatment of CNS disorders has increased the interest for these types of compounds. In this review, we highlight recent progress in the clinical development of NAS drug candidates, in addition to preclinical breakthroughs in the identification of novel NASs, mainly for GABA and NMDA receptor modulation.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso Central/tratamento farmacológico
Descoberta de Drogas
Neurotransmissores/farmacologia
Receptores de GABA-A/metabolismo
Receptores de N-Metil-D-Aspartato/metabolismo
[Mh] Termos MeSH secundário: Animais
Doenças do Sistema Nervoso Central/metabolismo
Relação Dose-Resposta a Droga
Seres Humanos
Conformação Molecular
Neurotransmissores/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Neurotransmitter Agents); 0 (Receptors, GABA-A); 0 (Receptors, N-Methyl-D-Aspartate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


  7 / 18006 MEDLINE  
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[PMID]:29244810
[Au] Autor:Bliss DP; D'Esposito M
[Ad] Endereço:Helen Wills Neuroscience Institute, University of California, Berkeley, CA, United States of America.
[Ti] Título:Synaptic augmentation in a cortical circuit model reproduces serial dependence in visual working memory.
[So] Source:PLoS One;12(12):e0188927, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent work has established that visual working memory is subject to serial dependence: current information in memory blends with that from the recent past as a function of their similarity. This tuned temporal smoothing likely promotes the stability of memory in the face of noise and occlusion. Serial dependence accumulates over several seconds in memory and deteriorates with increased separation between trials. While this phenomenon has been extensively characterized in behavior, its neural mechanism is unknown. In the present study, we investigate the circuit-level origins of serial dependence in a biophysical model of cortex. We explore two distinct kinds of mechanisms: stable persistent activity during the memory delay period and dynamic "activity-silent" synaptic plasticity. We find that networks endowed with both strong reverberation to support persistent activity and dynamic synapses can closely reproduce behavioral serial dependence. Specifically, elevated activity drives synaptic augmentation, which biases activity on the subsequent trial, giving rise to a spatiotemporally tuned shift in the population response. Our hybrid neural model is a theoretical advance beyond abstract mathematical characterizations, offers testable hypotheses for physiological research, and demonstrates the power of biological insights to provide a quantitative explanation of human behavior.
[Mh] Termos MeSH primário: Córtex Cerebral/fisiologia
Memória de Curto Prazo/fisiologia
Modelos Neurológicos
Transmissão Sináptica/fisiologia
Vias Visuais/fisiologia
[Mh] Termos MeSH secundário: Córtex Cerebral/citologia
Simulação por Computador
Seres Humanos
Plasticidade Neuronal/fisiologia
Células Piramidais/citologia
Células Piramidais/fisiologia
Receptores de AMPA/fisiologia
Receptores de GABA-A/fisiologia
Receptores de N-Metil-D-Aspartato/fisiologia
Sinapses/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, AMPA); 0 (Receptors, GABA-A); 0 (Receptors, N-Methyl-D-Aspartate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188927


  8 / 18006 MEDLINE  
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[PMID]:29216332
[Au] Autor:Kanatani S; Fuks JM; Olafsson EB; Westermark L; Chambers B; Varas-Godoy M; Uhlén P; Barragan A
[Ad] Endereço:Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
[Ti] Título:Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii.
[So] Source:PLoS Pathog;13(12):e1006739, 2017 Dec.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon T. gondii-infection, γ-aminobutyric acid (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC hypermotility and transmigration in vitro. We report that activation of GABAA receptors by GABA induces transient Ca2+ entry in DCs. Murine bone marrow-derived DCs preferentially expressed the L-type voltage-dependent Ca2+ channel (VDCC) subtype Cav1.3. Silencing of Cav1.3 by short hairpin RNA or selective pharmacological antagonism of VDCCs abolished the Toxoplasma-induced hypermigratory phenotype. In a mouse model of toxoplasmosis, VDCC inhibition of adoptively transferred Toxoplasma-infected DCs delayed the appearance of cell-associated parasites in the blood circulation and reduced parasite dissemination to target organs. The present data establish that T. gondii-induced hypermigration of DCs requires signaling via VDCCs and that Ca2+ acts as a second messenger to GABAergic signaling via the VDCC Cav1.3. The findings define a novel motility-related signaling axis in DCs and unveil that interneurons and DCs share common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical pathways to induce host cell migration and facilitate dissemination.
[Mh] Termos MeSH primário: Canais de Cálcio Tipo L/imunologia
Sinalização do Cálcio
Células Dendríticas/imunologia
Receptores de GABA-A/imunologia
Toxoplasma/imunologia
Toxoplasmose/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Movimento Celular
Células Cultivadas
Células Dendríticas/parasitologia
GABAérgicos/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Toxoplasma/fisiologia
Toxoplasmose/parasitologia
Ácido gama-Aminobutírico/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cacna1d protein, mouse); 0 (Calcium Channels, L-Type); 0 (GABA Agents); 0 (Receptors, GABA-A); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006739


  9 / 18006 MEDLINE  
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[PMID]:29184199
[Au] Autor:Sommeijer JP; Ahmadlou M; Saiepour MH; Seignette K; Min R; Heimel JA; Levelt CN
[Ad] Endereço:Department of Molecular Visual Plasticity, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
[Ti] Título:Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus.
[So] Source:Nat Neurosci;20(12):1715-1721, 2017 Dec.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.
[Mh] Termos MeSH primário: Período Crítico (Psicologia)
Plasticidade Neuronal/fisiologia
Tálamo/fisiologia
Córtex Visual/fisiologia
[Mh] Termos MeSH secundário: Animais
Dominância Ocular/fisiologia
Fenômenos Eletrofisiológicos
Olho/crescimento & desenvolvimento
Lateralidade Funcional/fisiologia
Corpos Geniculados/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Estimulação Luminosa
Receptores de GABA-A/deficiência
Receptores de GABA-A/genética
Visão Binocular/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gabra1 protein, mouse); 0 (Receptors, GABA-A)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1038/s41593-017-0002-3


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[PMID]:29032150
[Au] Autor:Sundararajan T; Manzardo AM; Butler MG
[Ad] Endereço:Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS, United States.
[Ti] Título:Functional analysis of schizophrenia genes using GeneAnalytics program and integrated databases.
[So] Source:Gene;641:25-34, 2018 Jan 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Schizophrenia (SCZ) is a chronic debilitating neuropsychiatric disorder with multiple risk factors involving numerous complex genetic influences. We examined and updated a master list of clinically relevant and susceptibility genes associated with SCZ reported in the literature and genomic databases dedicated to gene discovery for characterization of SCZ genes. We used the commercially available GeneAnalytics computer-based gene analysis program and integrated genomic databases to create a molecular profile of the updated list of 608 SCZ genes to model their impact in select categories (tissues and cells, diseases, pathways, biological processes, molecular functions, phenotypes and compounds) using specialized GeneAnalytics algorithms. Genes for schizophrenia were predominantly expressed in the cerebellum, cerebral cortex, medulla oblongata, thalamus and hypothalamus. Psychiatric/behavioral disorders incorporating SCZ genes included ADHD, bipolar disorder, autism spectrum disorder and alcohol dependence as well as cancer, Alzheimer's and Parkinson's disease, sleep disturbances and inflammation. Function based analysis of major biological pathways and mechanisms associated with SCZ genes identified glutaminergic receptors (e.g., GRIA1, GRIN2, GRIK4, GRM5), serotonergic receptors (e.g., HTR2A, HTR2C), GABAergic receptors (e.g., GABRA1, GABRB2), dopaminergic receptors (e.g., DRD1, DRD2), calcium-related channels (e.g., CACNA1H, CACNA1B), solute transporters (e.g., SLC1A1, SLC6A2) and for neurodevelopment (e.g., ADCY1, MEF2C, NOTCH2, SHANK3). Biological mechanisms involving synaptic transmission, regulation of membrane potential and transmembrane ion transport were identified as leading molecular functions associated with SCZ genes. Our approach to interrogate SCZ genes and their interactions at various levels has increased our knowledge and insight into the disease process possibly opening new avenues for therapeutic intervention.
[Mh] Termos MeSH primário: Estudo de Associação Genômica Ampla
Transporte de Íons/genética
Potenciais da Membrana/genética
Esquizofrenia/genética
Transmissão Sináptica/genética
[Mh] Termos MeSH secundário: Sistemas de Transporte de Aminoácidos/genética
Canais de Cálcio/genética
Cerebelo/citologia
Córtex Cerebral/citologia
Bases de Dados Genéticas
Seres Humanos
Hipotálamo/citologia
Bulbo/citologia
Receptores Dopaminérgicos/genética
Receptores de GABA-A/genética
Receptores Ionotrópicos de Glutamato/genética
Receptores de Serotonina/genética
Tálamo/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport Systems); 0 (Calcium Channels); 0 (Receptors, Dopamine); 0 (Receptors, GABA-A); 0 (Receptors, Ionotropic Glutamate); 0 (Receptors, Serotonin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE



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