Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory.
Nat Neurosci
; 17(1): 97-105, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24292233
ABSTRACT
Tumor necrosis factor α (TNF) is a proinflammatory cytokine with established roles in host defense and immune system organogenesis. We studied TNF function and found a previously unidentified physiological function that extends its effect beyond the host into the developing offspring. A partial or complete maternal TNF deficit, specifically in hematopoietic cells, resulted in reduced milk levels of the chemokines IP-10, MCP-1, MCP-3, MCP-5 and MIP-1ß, which in turn augmented offspring postnatal hippocampal proliferation, leading to improved adult spatial memory in mice. These effects were reproduced by the postpartum administration of a clinically used anti-TNF agent. Chemokines, fed to suckling pups of TNF-deficient mothers, restored both postnatal proliferation and spatial memory to normal levels. Our results identify a TNF-dependent 'lactrocrine' pathway that programs offspring hippocampal development and memory. The level of ambient TNF is known to be downregulated by physical activity, exercise and adaptive stress. We propose that the maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to post-weaning environmental challenges and competition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Fator de Necrose Tumoral alfa
/
Leite
/
Hipocampo
/
Memória
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos