Malnutrição protéica e desenvolvimento hipocampal: estudo das implicações sobre memória/aprendizado e avaliação da distribuição da Óxido Nítrico Sintase

• Autor(a) principal: Lotufo, Bruna Messias
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/16254
• topic: Malnutrition; Hippocampus; Memory and learning; Nitric Oxide; Desnutrição; Hipocampo; NADPH-d; Memória e aprendizado; Desnutrição; Hipocampo (Cérebro); Óxido nítrico sintase; Desenvolvimento cognitivo; Desnutrição Proteico-Calórica; Cérebro Desnutrição; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA

Undernutrition is one of the main epigenetic factors that affect brain development. The hippocampus is a very vulnerable structure that is selectively affected by alterations of food intake during the developmental period. Nitric oxide synthase is an enzyme highly expressed in this structure and nitric oxide has been postulated to have a role in hippocampal LTP and LTD. Here, we evaluated, in rats, the effects of protein malnutrition during the first 10 days of lactation on the distribution of NADPH-diaphorase and on the following behaviors: anxiety, novelty seeking and memory/learning. This study was approved by our University Ethics Committee (CEA/055/2009). Wistar male rats were divided into two groups: control group (CG) and malnourished group (MG). Dams were fed ad libitum with a normoprotein diet (22% protein) during gestation. During the first 10 days of lactation, MG dams received a protein free (0% protein) diet while CG dams received a normoprotein (22%protein) diet. After P10, all dams were fed with a normoprotein diet. On each age studied, P10 until P90 (n=5 for each group), the animals brains were processed histologically and then NADPH-d histochemistry was carried out. Behavioral tests were performed with one male from each litter. Anxiety-like effects were measured in the elevated plus maze (EPM) during 5 min. The time spent in and entries into the open arms were the measured variables. The hole board (HB) was used to assess novelty-seeking (number of nose pokes) for 5 min. Memory and learning were assessed in the 8-arm radial water maze (8-ARWM). The time needed to find a small platform (4 trials/day for 5 consecutive days) submerged in cloudy water was the measured variable. P10 MG animals showed more stained NADPH-d+ cells on the dentate gyrus. At P20, we observed fewer stained cells in MG and this pattern was also observed at P30 and P45. At P90 the staining pattern in the dentate gyrus was similar for both groups. P10 MG animals showed less stained cell bodies in the stratum pyramidale. At P20, the stratum pyramidale in both groups showed intense staining. P30 MG animals showed more stained NADPH-d cells, but, at P45, we observed few stained cells in both groups. Though P90 MG animals presented more stained cells in stratum pyramidale. No differences between groups were observed regarding the anxiety measures. Regarding novelty-seeking, P90 MG animals presented a significantly (ANOVA: P=0.014 and 0,017) higher number of nose pokes that CG ones. No differences were found between groups at P40. As for memory/learning, P90 MG animals had a significantly (P=0.032) reduced latency to find the platform than CG ones in the 8-ARWM. No differences were found between groups at P40. Our results demonstrate that protein malnutrition restricted to the first 10 days of lactation altered the distribution of NADPH-d on hippocampus. The malnourished animals did not display behavioral alterations at P40. Conversely, P90 malnourished animals displayed higher levels of novelty-seeking behavior and a better memory/learning performance, mainly in the first testing day, suggesting that the effect is highly dependent on the novelty of the testing situation.