Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory.
Nat Neurosci
; 17(1): 97-105, 2014 Jan.
Article
en En
| MEDLINE
| ID: mdl-24292233
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
Base de datos:
MEDLINE
Asunto principal:
Citocinas
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Factor de Necrosis Tumoral alfa
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Leche
/
Hipocampo
/
Memoria
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
Nat Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos