miRNA Profile in Hippocampus, Prefrontal Cortex and Sperm of Spontaneously Hypertensive Rats (SHR), a Model for Schizophrenia

Abstract

Gabriella Mesas Campagnoli, Isabelle Hernandez Cantão, Maryana Mara Marins, Agatha Ribeiro Mendes, Beatriz Ribeiro Nogueira, Renan Paulo Martin, João Bosco Pesquero, Taiza Stumpp

Environment is crucial for manifestation and development of schizophrenia, bringing to light epigenetic mechanisms involved, such as post-transcriptional control of gene expression by miRNA, in this disorder. MiRNAs participate in physiological processes such as neurogenesis, behavioral manifestations as well as in adverse conditions like psychiatric disorders. Experimental models are essential to investigate the development of schizophrenia from early life, especially its molecular aspects.Spontaneously hypertensive rats (SHR) are considered a good model for schizophrenia, since they show behavior that can be related to SCZ symptoms in humans and respond to treatment with anti-psychotic drugs. We investigated miRNA profile in prefrontal cortex, hippocampus and sperm of SHR through next generation sequencing (NGS). SHR showed differential expression (DE) of miRNAs related to neurological processes and schizophrenia in sperm, prefrontal cortex and hippocampus. Gene ontology and enrichment analyses showed that the majority of DE miRNA target genes are involved in pathways related to behavior, neurodevelopment and synaptic processes. Among these genes, 12 are dysregulated in schizophrenia patients, what reinforces SHR as a good model for epigenetic and molecular studies of this disorder. Finally, altered miRNA expression in sperm suggests that SHR model may be useful for future studies on epigenetic inheritance of schizophrenia.

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