Perinatal and adolescent protein malnutrition have different effects on cognition in adult mice

CHERTOFF, MARIELA; BALLARINI, FABRICIO; IGAZ, LIONEL M.; BERARDINO BRUNO; CÁNEPA EDUARDO TOMÁS

Congreso; XXXIV ANUAL MEETING SAN 2019; 2019

P135.-Altered gene expression in medial prefrontal cortex correlates with social cognition deficits derived from perinatal malnutrition in a mouse modelEstefanía A. Fesser1, Octavio Gianatiempo1, María Fernanda Trejo Martinez2 Bruno G. Berardino1, Eduardo T. Cánepa11 Laboratorio de Neuroepigenética, Departamento de Química Biológica e IQUIBICEN, FCEyN, UBA-CONICET 2Instituto Nacional de Medicina Genomica, Ciudad de MéxicoPresenting author: Estefanía Aylén Fesser, estefaniafesser@gmail.comEarly life adversities such as perinatal malnutrition can modulate neuronal plasticity contributing to neurophysiologic and behavioral alterations. However, mechanisms mediating these effects are not completely known. The aim of this work was to evaluate the impact of perinatal malnutrition on social cognition. We used CF1 dams fed with normal (NP, casein 20%) or low protein diet (LP, casein 8%) during pregnancy and lactation. Offspring were analyzed at PD56. Preclinical PET analysis showed an altered activity in the prefrontal cortex (mPFC) of LP mice suggesting a deficit in the function of this brain?s region. The mPFC is involved in the regulation of social cognition. We found that contextual recognition memory, social interaction and social memory were impaired in LP mice. Besides, LP mice exhibited an increased dominance hierarchy. To investigate the potential contribution of E/I imbalance in the mPFC to these behaviors, we evaluate the expression of genes involved in Gabaergic and Glutamatergic transmission. LP mice expressed higher levels of Gria1 and Vglut1 than their NP counterparts. In addition, expression of HDAC2, 5, 7, 10 and 11 were decreased in LP mice. Immunoblot analysis revealed global changes in repressive histone marks H3K9me3 and H3K27me3 and activator mark H3K4me3. We propose that alteration of epigenetic mechanisms during brain development caused by perinatal malnutrition could lead to altered E/I balance and subsequent deficits in the social domain.