IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Prenatal inflammation alters the immune hippocampal microenvironment and impairs adult neurogenesis
Autor/es:
GRACIARENA M; BATTISTA D; FERRARI C,; PITOSSI F
Lugar:
Rio de Janeiro
Reunión:
Congreso; International Society of Neuroimmunomodulation; 2008
Institución organizadora:
International Society of Neuroimmunomodulation
Resumen:
Introduction The perinatal stage is characterized by sensitivity to certain stimuli that will be reflected in the adult. As it is reported that prenatal exposure to lipopolysaccharide (LPS), a well known cytokine inducer, provokes long-lasting changes in corticosterone and can cross the blood brain barrier at this stage consequently altering the hippocampal microenvironment, we hypothesized that prenatal LPS could affect adult neurogenesis through any of these mechanisms. Methodology Pregnant Wistar rats were injected subcutaneously with LPS  (0,5 mg/kg) over the last week of pregnancy, and effects were studied in the adult litter. LPS was also injected in some adult rats. Adult rats were injected with bromodeoxyuridine (BrdU) for 7 days, and perfused. Neurogenesis/progenitor proliferation were assessed by colabelling BrdU and neuronal/progenitor markers respectively. Microglial activation was assessed classifying the morphology of GSA positive cells. Corticosterone levels were assessed by RIA. Cytokine expression levels were determined by real time PCR. Results Impaired adult neurogenesis was observed in prenatal LPS-treated rats. Adult LPS did not further diminish neurogenesis in this group. Microglial activation was observed in prenatal, adult, and prenatal+adult LPS group. Basal corticosterone levels were equal in prenatal LPS or Saline rats, but adult LPS caused a longer corticosterone increase in the prenatal LPS-treated group. Altered cytokine expression was observed in fetal and neonatal brain of LPS-treated group. Conclusions Prenatal LPS challenge impairs adult neurogenesis, this effect may not be mediated by corticosterone, and may involve changes in the local environment, in which proinflammatory cytokines are involved.