Padrão de distribuição de moléculas orexigênicas em vias hipotalâmicas reguladoras da ingestão alimentar em animais malnutridos durante a lactação

Abstract

In the CNS the hypothalamus is the region responsible for energetic alterations perception. Among its several nuclei, arcuate (ARC) nucleus is the first one to detect and transmit these alterations to other hypothalamic nuclei trough two neuronal populations: orexigenic neuropeptide Y/agouti related protein (NPY/AgRP) neurons and anorexigenic pro-opiomelanocortin/cocaine-amphetamine regulated transcript neurons (POMC/CART). Studies using the 0% protein diet during the first 10 lactation days protocol showed that animals developed leptin resistance, hiperinsulinism and obesity in adulthood. In our laboratory we also observed alterations in nitric oxide synthase distribution. The aim of this work was to study the effects of this same diet protocol in hypothalamic cell density and NPY/AgRP expression. Wistar offspring were adjusted to 6 pups per dam after parturition. We used rats from 5 to 45 postnatal (P) days of age whose dams were either fed a 0% protein diet or a normoprotein diet from P1 to P10. After the 10th lactation day all dams were given the normoprotein diet. All animals were anesthetized and intracardially perfused-fixated between 9:00h-11:00h AM. Brains were sectioned at a cryostat in the coronal plane at 20 μm. Immunohistochemistry techniques were performed to access NPY and AgRP expression in hypothalamic nuclei involved in energetic metabolism regulation. Some sections were stained with DAPI. Our results showed a decrease in cell density between P10 and P30 in control group animals (GC), notwithstanding, malnourished group anumals (GM) presented higher cell densities in the ventral and dorsal portions of the dorsomedial hypothalamic nucleus (DMH) and in the lateral hypothalamic nucleus (LH) by P30 than the GC. NPY and AgRP distribution also presented differences between both groups. Between P10 and P20, a critical window in hypothalamic orexigenic pathways maturation, we observed an increase in NPY expression in several hypothalamic nuclei as the paraventricualr (PVN), DMH, ARC in GM animals and higher expression of AgRP in PVN but lesser in DMH and LH, in those animals. Our results showed alterations in cell density and expression of key molecules in hypothalamic metabolic control due to malnutrition during part of the lactation period. These alterations during a critical moment in development could lead to permanent changes in feeding behavior by these animals.