LSD1/LSD1-8a altered ratio in a rat model of neurodevelopment disorder? Perinatal Hy-poxia as animal models of gene-environment interaction in schizophrenia

MARTIN BUSTELO TEJADA1, FABIÁN LOIDL2 AND MARTIN A. BRUNO

Buenos Aires

Conferencia; Conference of Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN); 2016

FALAN

Schizophrenia (SCZ) has long been considered as a disorder with multifactorial ori-gins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritabil-ity estimates suggest an important contribution of non-genetic factors. Various envi-ronmental risk factors have been proposed to play a role in the etiopathogenesis of SCZ. We still have a limited understanding of the mechanisms whereby gene-environment interactions (GxE) operate in SCZ. Here we investigate an animal model of GxE interaction as a paradigm of adverse event at perinatal stage leading to ab-normal neural maturation, associated with neurological disorders. Regarding specifi-cally gene expression programs in neurons, Lysine-specific demethylase 1 (LSD1) is a histone demethylase that has been proposed to acts as a key transcriptional co-repressor. In mammalian brain, alternative splicing of LSD1 mini-exon E8a gives rise to neuroLSD1, a neurospecific isoform. Here we show that the LSD1/LSD1-8a ratio and LSD1 expression levels changes in response to hypoxia and such effect is mediated by the miR-137, an known hipoxamir targeting LSD1; strengthening the evidence that hypoxia affects the normal neuronal radial migration. Using behavioral and micro-scope analyses we are correlating LSD1/LSD1-8a mRNA and protein levels with cogni-tive and anatomical deficits at adult stage of our experimental model of SCZ GxE interaction.