Studies conducted in rodents subjected to chronic stress and some observations
in humans after psychosocial stress, have allowed to establish a link between
stress and the susceptibility to many complex diseases, including mood
disorders. The studies in rodents have revealed that chronic exposure to stress
negatively affects synaptic plasticity by triggering changes in the production
of trophic factors, subunit levels of glutamate ionotropic receptors, neuron
morphology, and neurogenesis in the adult hippocampus. These modifications may
account for the impairment in learning and memory processes observed in
chronically stressed animals. It is plausible then, that stress modifies the
interplay between signal transduction cascades and gene expression regulation in
the hippocampus, therefore leading to altered neuroplasticity and functioning of
neural circuits. Considering that miRNAs play an important role in
post-transcriptional-regulation of gene expression and participate in several
hippocampus-dependent functions; we evaluated the consequences of chronic stress
on the expression of miRNAs in dorsal (anterior) portion of the hippocampus,
which participates in memory formation in rodents. Here, we show that male rats
exposed to daily restraint stress (2.5 h/day) during 7 and 14 days display a
differential profile of miRNA levels in dorsal hippocampus and remarkably, we
found that some of these miRNAs belong to the miR-379-410 cluster. We confirmed
a rise in miR-92a and miR-485 levels after 14 days of stress by qPCR, an effect
that was not mimicked by chronic administration of corticosterone (14 days). Our
in silico study identified the top-10 biological functions influenced by
miR-92a, nine of which were shared with miR-485: Nervous system development and
function, Tissue development, Behavior, Embryonic development, Organ
development, Organismal development, Organismal survival, Tissue morphology, and
Organ morphology. Furthermore, our in silico study provided a landscape of
potential miRNA-92a and miR-485 targets, along with relevant canonical pathways
related to axonal guidance signaling and cAMP signaling, which may influence the
functioning of several neuroplastic substrates in dorsal hippocampus.
Additionally, the combined effect of miR-92a and miR-485 on transcription
factors, along with histone-modifying enzymes, may have a functional relevance
by producing changes in gene regulatory networks that modify the neuroplastic
capacity of the adult dorsal hippocampus under stress.
