Enhanced neuronal loss under perinatal hypothyroidism involves impaired neurotrophic signaling and increased proteolysis of p75(NTR).
Mol Cell Neurosci
; 40(3): 354-64, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19138744
ABSTRACT
Recognition of the molecular events that lead to enhanced cell death is vital to understand the developmental cerebellar defects under hypothyroidism. Though neurotrophins promote the survival and development of neurons in the cerebellum, but the mechanism of their insufficiency mediated cell loss under hypothyroidism is unknown. Here in developmental hypothyroid rat model we report that hypothyroidism induced neuronal loss involve down regulation of neurotrophic survival signaling and increased truncation of the receptor p75(NTR). Results showed that perinatal hypothyroidism besides repressing the expression of BDNF also impairs the maturation of NGF which results in decreased activation of ERK, CREB, NF-kappaB and AKT. Furthermore hypothyroidism caused an enhanced expression and proteolysis of p75(NTR). The increased proteolysis of p75(NTR)in vivo and its association with death of granule neurons brings forward hitherto a p75(NTR) dependence signaling which along with compromised survival signaling could provide a neurotrophic basis of understanding the cause of enhanced cell death in developing cerebellum under hypothyroidism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Receptores de Fator de Crescimento Neural
/
Hipotireoidismo
/
Fatores de Crescimento Neural
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA