06 agosto 2018

MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology.

DOI : 10.3389/fnmol.2018.00251

Elena Vidal

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.

Investigadores Participantes del Centro

Laboratorio de Genómica y Biología de Sistemas Vegetales (PlantomicsLab)

Doctora en Ciencias Biológicas, Pontificia Universidad Católica de Chile.



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