Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein.
Stem Cell Reports
; 11(6): 1449-1461, 2018 12 11.
Article
en En
| MEDLINE
| ID: mdl-30503263
ABSTRACT
The absence of FMR1 protein (FMRP) causes fragile X syndrome (FXS) and disturbed FMRP function is implicated in several forms of human psychopathology. We show that intracellular calcium responses to depolarization are augmented in neural progenitors derived from human induced pluripotent stem cells and mouse brain with FXS. Increased calcium influx via nifedipine-sensitive voltage-gated calcium (Cav) channels contributes to the exaggerated responses to depolarization and type 1 metabotropic glutamate receptor activation. The ratio of L-type/T-type Cav channel expression is increased in FXS progenitors and correlates with enhanced progenitor differentiation to glutamate-responsive cells. Genetic reduction of brain-derived neurotrophic factor in FXS mouse progenitors diminishes the expression of Cav channels and activity-dependent responses, which are associated with increased phosphorylation of the phospholipase C-γ1 site within TrkB receptors and changes of differentiating progenitor subpopulations. Our results show developmental effects of increased calcium influx via L-type Cav channels in FXS neural progenitors.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Calcio
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Canales de Calcio Tipo L
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
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Células-Madre Neurales
Límite:
Animals
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Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2018
Tipo del documento:
Article
País de afiliación:
Finlandia