Gender-specific modulation of glucocorticoid receptor and MeCP2 by perinatal protein malnutrition and postnatal environment in mice.

CHERTOFF MARIELA; ALBERCA CAROLINA; BERARDINO BRUNO; CÁNEPA EDUARDO TOMÁS

Rio de Janeiro

Congreso; 9th Wordl IBRO Congress; 2015

IBRO

Gender-specific modulation of  glucocorticoid receptor and MeCP2 by perinatal protein malnutrition and postnatal environment  in mice. Mariela Chertoff, Carolina Alberca, Bruno Berardino and Eduardo Cánepa Laboratorio de Neuroepigenetica - Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales - Universidad de Buenos Aires - CONICET Poor nutrition during early period of life results in improper development of the brain. Previous results of our group demonstrate a delay on development parameters such as outer ear detachment, opening of auditory pavilion and sound, tactile and visual reflex. In addition, protein malnutrition promotes anxiety and depression-related behaviors on littermates in a gender-dependent manner. These changes extend thepostnatal period and continue throughoutadulthood; however, the molecular mechanisms involved on this process are poorly understood. Moreover, malnourished dams show reduced maternal care and anxiety-like behavior. We focus our study on the consequences of poor protein nutrition on methylation machinery and stress related molecules. The experimental design includes 2 groups of CF-1 dam mice: normal nourished dams (20% protein) and low-protein malnourished dams (8% of protein) from 5 days before mating to the end of lactation. In order to evaluate how post-weaning environment may epigenetically modulate gene expression, animals of both sexes were housing during 5 weeks after weaning in three different environments: 1-normal (4 animals/cage); 2-enriched (8 animals in a large cage with toys); and 3- impoverished (1 animal/cage with less bedding). We evaluate by qPCR the changes on expression of glucocorticoid receptor (GR), MeCP2 and methylation machinery members at hippocampus of littermates after weaning and after 5 weeks on different environments. We observed a reduction of GR expression in control females housing on impoverished compared to  normal environment. At weaning, MeCP2 decrease on hippocampus of malnourished female pups (P: 0.0286, Mann-Whitney test). Interestingly, no changes are observed in males suggesting a gender-bias on regulation of these molecules. In conclusion, maternal malnutrition affects brain development with long-lasting behavioral consequences. However, the stress response seems to be more affected by postnatal environment than by perinatal nutrition. In contrast, epigenetic machinery is likely to respond to diet without being disturbed by environment after weaning.