IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Differential effects of prenatal vs adult inflammatory stimuli on adult neurogenesis and the neurogenic niche
Autor/es:
VALERIA ROCA; MARIANA GRACIARENA; MATHIEU, PATRICIA; F.J. PITOSSI
Lugar:
Yokohama
Reunión:
Congreso; 9TH Annual Meeting of the International Society for Stem Cell Research; 2012
Institución organizadora:
ISSCR
Resumen:
Differential effects of prenatal vs adult inflammatory stimuli on adult neurogenesis and the neurogenic niche. Valeria Roca, Mariana Graciarena, Patricia Mathieu, Fernando Pitossi. Fundacion Instituto Leloir - CONICET, Buenos Aires, Argentina The perinatal stage is characterized by increased sensitivity to inflammatory stimuli which affect adult physiology, including adult neurogenesis. We have hypothesized that a prenatal pro-inflammatory challenge would cause a more sustained negative effect on adult neurogenesis than an adult one. To test this hypothesis, we injected Wistar pregnant rats subcutaneously with lipopolysaccharide (LPS, 0.5 mg/kg) or saline at embryonic days 14, 16, 18 and 20. In the adulthood, a similar regime (4 subcutaneous LPS injections every other day, 1 mg/kg) or a single ip. LPS dose (1 mg/kg) were administered. The effects on neurogenesis were assessed 60 days later in both cases. We have observed 25% reduction of adult neurogenesis levels and an impaired performance in the novel object recognition test in prenatally LPS-treated rats compared to controls. Both effects were mediated by a decrease in the levels of TGF-beta and accompanied by a long-term microglial activation in the dentate gyrus. In contrast, we found that adult LPS treatment significantly decreased adult neurogenesis after 7 days but not after 60 days, assessed by co-labeling of BrdU and neuronal markers (PSA-NCAM; DCX). In line with these results, microglial activation in adult LPS treated animals was only observed in correlation with decreased neurogenesis. Even though, cytokine expression analysis by real-time RT-PCR revealed a decrease in TGF-beta expression in the adult hippocampi of prenatally LPS-treated rats, the levels of TGF-beta expression in the DG of the adult treated animals remained unchanged. Hence, peripheral inflammation has different outcomes regarding adult neurogenesis and the neurogenic niche, according to the developmental stage when the challenge is received. These results highlight the susceptibility of the CNS to prenatal programming and its long term consequences compared to the limited response of the adult brain.