microRNA and mRNA profiles in nucleus accumbens underlying depression versus resilience in response to chronic stress

Abstract

Major depression in negative mood is presumably induced by chronic stress with lack of reward. However, most individuals who experience chronic stress demonstrate resilience. Molecular mechanisms underlying stress‐ induced depression versus resilience remain unknown, which are investigated in brain reward circuits. Mice were treated by chronic unpredictable mild stress (CUMS) for 4 weeks. The tests of sucrose preference, Y‐maze, and forced swimming were used to identify depression‐like emotion behavior or resilience. High‐throughput sequencing was used to analyze mRNA and miRNA quantity in the nucleus accumbens (NAc) harvested from the mice in the groups of control, CUMS‐induced depression (CUMS‐MDD), and CUMS‐resistance to identify molecular profiles of CUMS‐MDD versus CUMS‐resilience. In data analyses and comparison among three groups, 1.5‐fold ratio in reads per kilo‐base per million reads (RPKM) was set to judge involvements of mRNA and miRNA in CUMS, MDD, or resilience. The downregulations of serotonergic/dopaminergic synapses, MAPK/calcium signaling pathways, and morphine addiction as well as the upregulations of cAMP/PI3K‐Akt signaling pathways and amino acid metabolism are associated with CUMS‐MDD. The downregulations of chemokine signaling pathway, synaptic vesicle cycle, and nicotine addiction as well as the upregulations of calcium signaling pathway and tyrosine metabolism are associated with CUMS‐resilience. The impairments of serotonergic/dopaminergic synapses and PI3K‐Akt/MAPK signaling pathways in the NAc are associated with depression. The upregulation of these entities is associated with resilience. Consistent results from analyzing mRNA/miRNA and using different methods validate our finding and conclusion.

mRNA and microRNA profiles in the amygdala are relevant to Susceptible and Resilient mice induced by psychological stress

“…Stress types include physical stress versus psychological stress as well as acute severe stress versus chronic mild stress [31,32,48,55]. After undergoing psychological stress, stressors can be divided into stress susceptibility and stress resilience according to the different effects of stressors' physical and mental health.…”

“…Evidence indicates that several hormones and neurotransmitter systems(such as the norepinephrine system, the GABAergic system, the serotonin system, the endocannabinoid system, the glucocorticoid system, etc.) were modulated in the amygdala during or after stress stimuli [24][25][26][27][28][29][30][31][32]. Changes in the hormone and neurotransmitter systems further contribute to the amygdala's plasticity at the cellular and neural circuits levels [33,34].…”

Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

“…Quantitative real-time RT-PCR (qRT-PCR) were performed with the Bio-Rad CFX 96Touch as previously described [47]. Briefly, total RNA was extracted from mPFC with a TRIzol Kit.…”

Pronounced Inter-Individual Variation in Plasma Cortisol Response to Fluoxetine Hydrochloride in the Pig

“…However, these methods are less suited to a production environment, because they are time-consuming and arguably subjective [2,3]. There is, therefore, an urgent need to identify and validate novel physiological and molecular markers of positive affect, such as miRNA [4,5], to complement or even replace behavioral [6] measures.…”