SeparaÃÃo materna prolongada induz desnutriÃÃo e inflamaÃÃo sistÃmica com deficiÃncia de IGF-1 e leptina e alteraÃÃes hipocampais em camundongos lactentes

• Autor(a) principal: Ãtalo Leite Figueiredo
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
• Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=15641
• topic: CIENCIAS BIOLOGICAS

Prolonged maternal separation (PMS) can cause protein-energy malnutrition due to restriction of breast milk, which may lead to changes in the hippocampus, affecting the intestinal barrier, inducing bacterial translocation and systemic inflammation. A recent study has documented a negative correlation between systemic inflammatory markers and insulin-like growth factor-1 (IGF-1) serum levels in malnourished stunted children. However, there is a gap of knowledge how systemic inflammation affects hippocampal development in malnourished animals. This study aimed to investigate the effect of PMS on physical development, ontogeny of some neonatal reflexes, and on hippocampal alterations in C57BL6J mice, including morphological, neurochemical, and brain plasticity markers, including synaptophysin (SYN) and myelin basic protein (MBP) expression. A second aim of this study was to evaluate serum levels of corticosterone, IGF-1, leptin, adiponectin and an acute phase protein, C-reactive protein (CRP), the latter as a systemic inflammatory marker. PMS was induced by isolating half of the littermates from the dam for defined periods (4 hours on day 4, 8 hours on day 5 and 12 hours thereafter) in an incubator box. Daily measurements of weight and tail length were recorded, the latter as an indication of linear growth. Tests to evaluate neonatal reflexes included cliff avoidance, surface righting, swimming behaviors and dorsal immobility, which were performed on days 6, 8, 10, 12 and 14. On day 14, pups were euthanized by decapitation to drawn blood for serum hormonal analyses and CRP by ELISA. Hippocampus were harvest for amino acid dosage by HPLC; immunohistochemistry for SYN; and total brain SYN and MBP by western blot. A subset of animals was subject to transcardiac perfusion with a fixative solution for stereological analyses. PMS induced malnutrition with significant reduction in body weight gain (from the sixth day) and tail length (from the eleventh day) (p<0.05). The assessment of neonatal reflexes revealed differences between groups on surface righting and dorsal immobility (p<0.05). The stereology data showed that malnutrition challenge reduced the total volume and area of the CA3 hippocampal field and CA3 pyramidal layer volume and reduced CA1 pyramidal layer area (p<0.05) when compared with the non-separated control group (NSC). The amino acid dosage indicated lower concentration of aspartate, glutamate, glycine and GABA in PMS when compared with CNS animals (p<0.05). The NSC mice showed more hippocampal SYN immunolabeling when compared with the PMS group. PMS mice had higher serum levels of IGF-1 and leptin, as well as increased serum CRP (p<0.05). Together, these results suggest that PMS causes systemic inflammation with reduced serum levels of leptin and IGF-1, growth and behavioral deficits, along with alterations in the hippocampal structure and neurochemical activity.