Ambiente enriquecido na prevenção dos prejuízos comportamentais e endócrinos no modelo de hiperleptinemia neonatal

Abstract

There is an important association between nutritional, hormonal and environmental parameters during early life (pregnancy and lactation periods) and development of chronic diseases during adult life such as: cardiovascular diseases, obesity, diabetes, anxiety and depression. Previously we demonstrated that rats treated with leptin injections (8µg/100g/day, sc) during the first 10 days of lactation presented increase of anxiety, exploratory activity, hyperleptinemia, overweight, leptin resistance, hyperinsulemia, hypercorticosteronemia and hypertrigliceridemia at adulthood. We propose to investigate, trough longitudinal study, behavioral and metabolic-endocrine programming caused by hyperleptinemia exposure during the first 10 days of lactation and evaluate if these changes can be prevented by exposure to enriched environment during adolescence period. Initially were obtained 2 experimental groups treated during the first 10 days of lactation (PN1-PN10) with: Saline (50µL/day, sc) or leptin (8µg/100g/day, sc). At PN30, some litters were allocated at new environment conditions (enriched environment cage), while other litters remained in a standard cage. Litters were subdivided into 4 groups: 1) C Group: Neonatal exposure to saline; 2) L Group: Neonatal exposure to leptin; 3) CEE Group: Neonatal exposure to saline and adolescent exposure to an enriched environment (PN30-PN45); 4) LEE Group: Neonatal exposure to leptin and adolescent exposure to an enriched environment. We evaluated the metabolic endocrine profile as well as anxiety-like and novelty-seeking behaviors using Elevated Plus Maze (EPM) and Hole Board (HB), respectively, before and after to enriched environment exposure. Regarding anxiety, it was initially observed an anxiolytic effect of leptin on PN21 and PN30, which was lost during development and contradictorily resulted in higher anxiety on PN150. Was observed a higher exploratory activity in PN30 and PN150. Behavioral disorders in adulthood were acompained by metabolic-endocrine dysfunction, such as: hyperleptinemia, overweight, leptin resistance, hypertrigliceridemia, hypercorticosteronemia and increase of free T4, which were prevented by enriched environment exposure during adolescence. Therefore, it was demonstrated that enriched environment exposure for 15 days during adolescence, showed itself a promising non-farmacologic treatment strategy in prevention of long-lasting behavioral and metabolic endocrine disorders induced by neonatal hyperletinemia.