Perinatal malnutrition deregulates PRC2 catalytic subunits and Kdm6b expression

FERRONI, NADINA M.; FESSER, ESTEFANÍA A.; CÁNEPA, EDUARDO T.; SONZOGNI, SILVINA V.

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

Sociedad Argentina de Neurociencias

Early life adversities such as perinatal malnutrition can modulate neuronal plasticity through epigenetic mechanisms contributing to neurophysiologic and behavioral alterations. However, factors mediating these effects remain still unknown.To evaluate these factors we used CF1 dams fed with normal protein diet (NP, casein 20%) or low protein diet (LP, casein 8%) during pregnancy and lactation, and the offspring were analyzed at P56. Using high-throughput sequencing we evaluated the global gene expression profile in medial prefrontal cortex (mPFC) of NP and LP mice. From the analysis of the RNA-seq, demethylase Kdm6b, methytransferases Ezh1 and Ezh2 (PRC2 subunits) and transcription factor Npas4 turned out to be interesting candidates for this study since methylation/demethylation of H3K27 and Npas4 pathway are involved in neurodevelopment and cognitive abilities. RT-qPCPR analysis showed that these four genes were differentially expressed in primary cultures of mouse embryonic fibroblasts (MEFs). Further, Kdm6b and Ezh1 expression were significantly decreased in the mPFC of LP female mice at P56. Predicted microRNAs that potentially regulate Kdm6b or Ezh1 mRNAs were analysed by stem-loop RT-qPCR. miR-138-5p, miR-20a-5p, miR135a-5p and miR-103-3p were not differentially expressed.These results suggest that perinatal malnutrition could affect epigenetic mechanisms, particularly histone methylation, that mediate the development and the cognitive and social deficits in later life.