Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms.
Mol Neurobiol
; 48(3): 590-600, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23564401
ABSTRACT
Calcium sensing receptor (CaSR) is implicated in the establishment of neural connections and myelin formation. However, its contribution to brain development remains unclear. We addressed this issue by analyzing brain phenotype in postnatal CaSR null mice, a model of human neonatal severe hyperparathyroidism. One- and 2-week-old CaSR null mice exhibited decreased brain weight and size with a developmental delay in expression of proliferating cell nuclear antigen. Neuronal and glial differentiation markers, neuronal specific nuclear protein, glial fibrillary acidic protein, and myelin basic protein, were also decreased compared with age-matched wild-type littermates. Moreover, deletion of the parathyroid hormone gene that corrects hyperparathyroidism, hypercalcemia, hypophosphatemia, and whole-body growth retardation normalized brain cell proliferation, but not differentiation, in CaSR null mice. Cultured neural stem cells (NSCs) derived from the subventricular zones of CaSR null neonatal mice exhibited normal proliferation capacity but decreased differentiation capacity, compared with wild-type controls. These results demonstrate that direct effects of CaSR absence impair NSC differentiation, while secondary effects of parathyroid hormone-related endocrine abnormalities impair NSC proliferation, both of which contribute to delayed brain development in CaSR null newborn mice.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Receptores de Detecção de Cálcio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article