IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effects of prenatal inflammation on adult neurogenesis: role of TGF-beta
Autor/es:
GRACIARENA M.,; DEPINO A.,; PITOSSI F.
Lugar:
BRASIL
Reunión:
Simposio; Simposio Internacional de Terapia Celular; 2009
Resumen:
Prenatal exposure to lipopolysaccharide (LPS), a well known cytokine inducer, is important to modulate adult physiology.In addition, we and others have observed that inflammation can diminish adult neurogenesis. We have hypothesized that a prenatal LPS challenge could alter the brain environment of endogenous neural stem cells and alter adult neurogenesis.To test this hypothesis, we injected Wistar pregnant rats subcutaneously with 0,5 mg/kg LPS or saline at embryonic days 14, 16, 18 and 20. At postnatal day 60, adult rats were injected i.p. with 50 mg/kg of bromodeoxyuridine (BrdU) daily for 7 days.We observed significantly reduced adult neurogenesis levels in prenatally LPS-treated rats compared to controls, as assessed by co-labeling of BrdU and neuronal markers (PSA-NCAM; DCX or NeuN). Proliferation of the progenitor cell population remained unchanged as measured by counting the number of BrdU-Nestin-positive cells. Moreover, adult microglial activation was observed only in the prenatally LPS-treated group. Cytokine expression analysis by real-time RT-PCR revealed a decrease in TGF-beta expression in the adult hippocampi of LPS-treated rats. Over-expression of TGF-beta in the adult hippocampi of prenatally LPS-treated rats not only reverted the decrease in adult neurogenesis but also return to basal levels the performance on a behavioural task associated with adult neurogenesis (Novel object recognition).We conclude that prenatal LPS challenge decreases adult neurogenesis and novel object recognition perfomance. This effect involves long lasting changes in the local microenvironment towards a pro- inflammatory mileu. TGF-beta plays a key role in the prenatally-induced decrease in adult neurogenesis.