Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Hippocampus ; 28(2): 97-107, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29116659

RESUMO

In the central nervous system, CaV 1.2 and CaV 1. 3 constitute the main L-type voltage-gated calcium channels (LTCCs) coupling membrane depolarization to gene transcription. We have previously demonstrated that inducible disruption of Cav1.2 in type-1 astrocyte-like stem cells of the adult dentate gyrus (DG) impairs hippocampal neurogenesis in a cell-autonomous fashion. To address the role of Cav1.3 channels (encoded by the Cacna1d gene), we here generated TgGLAST-CreERT2 /Cacna1dfl/fl /RCE:loxP mice which facilitate inducible deletion of Cacna1d in tandem with induction of EGFP expression in type-1 cells, allowing tracking of recombined cells and their descendants. Neurosphere cultures derived from fluorescence-activated cell sorting sorted Cacna1d-deficient (Cacna1d-/- /EGFP) hippocampal neural precursor cells (NPCs) exhibited a significant decrease in proliferative activity. Further, under differentiation conditions, Cacna1d deficiency conferred an increase in astrogenesis at the expense of neurogenesis. In like manner, type-1 cells lacking Cacna1d showed reduced proliferation in the dentate gyrus (DG) in vivo. Moreover, Cacna1d deficiency resulted in a significant decrease in the number of newly born cells adopting a neuronal fate. Finally, massive excitation induced by repeated electroconvulsive seizures rescued the proliferation defect of Cacna1d-/- /EGFP type-1 cells. Together, the effects of Cacna1d gene deletion closely recapitulate our earlier findings on the role of Cav1.2 channels expressed by type-1 cells. Similar to Cav1.2 channels, Cav1.3 channels on type-1 cells boost type-1 cell proliferation and promote subsequent neuronal fate choice.


Assuntos
Canais de Cálcio Tipo L/deficiência , Proliferação de Células/genética , Deleção de Genes , Neurônios/fisiologia , Animais , Canais de Cálcio Tipo L/genética , Diferenciação Celular , Células Cultivadas , Giro Denteado/citologia , Proteínas do Domínio Duplacortina , Estimulação Elétrica/efeitos adversos , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Transportador 1 de Aminoácido Excitatório/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Feminino , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/fisiologia , Neurogênese/genética , Neuropeptídeos/metabolismo
2.
Glia ; 65(5): 817-827, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28230278

RESUMO

Ca2+ is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created TgGLAST-CreERT2 /Cacna1cfl/fl /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c. The EGFP reporter was used to trace the progeny of recombined type-1 cells. FACS-sorted Cacna1c-deficient neural precursor cells from the dentate gyrus showed reduced proliferative activity in neurosphere cultures. Moreover, under differentiation conditions, Cacna1c-deficient NPCs gave rise to fewer neurons and more astroglia. Similarly, under basal conditions in vivo, Cacna1c gene deletion in type-1 cells decreased type-1 cell proliferation and reduced the neuronal fate-choice decision of newly born cells, resulting in reduced net hippocampal neurogenesis. Unexpectedly, electroconvulsive seizures completely compensated for the proliferation deficit of Cacna1c deficient type-1 cells, indicating that there must be Cav 1.2-independent mechanisms of controlling proliferation related to excitation. In the aggregate, this is the first report demonstrating the presence of functional L-type 1.2 channels on type-1 cells. Cav 1.2 channels promote type-1 cell proliferation and push the glia-to-neuron ratio in the direction of a neuronal fate choice and subsequent neuronal differentiation. Cav 1.2 channels expressed on NPCs and their progeny possess the ability to shape neurogenesis in a cell-autonomous fashion.


Assuntos
Canais de Cálcio Tipo L/genética , Hipocampo/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Animais , Diferenciação Celular/genética , Células Cultivadas , Camundongos Transgênicos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...