miR‑9 inhibition of neuronal apoptosis and expression levels of apoptosis genes Bcl‑2 and Bax in depression model rats through Notch pathway

Abstract

Effects of micro ribonucleic acid (miR)-9 on neuronal apoptosis and expression levels of apoptosis genes B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in depression model rats, as well as its regulatory mechanism, were investigated. Thirty Sprague-Dawley rats were randomly divided into control group (n=10), model group (n=10) and miR-9 inhibitor group (n=10). The rat model of depression was established using the chronic stress method. The learning and memory abilities of rats were detected via water maze test, the neuronal morphology of the brain was detected using hematoxylin and eosin (H&E) staining, and the levels of serum Bcl-2 and Bax were determined using the enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the neuronal apoptosis in the brain was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein levels of Notch1 and Hes1 in brain tissues were measured via western blot analysis. Compared with the control group, the rats in the model group presented significantly decreased learning and memory abilities, poor neuronal morphology of the brain, significantly higher neuronal apoptosis rate in the brain, decreased level of serum Bcl-2, increased level of serum Bax, and significantly decreased protein levels of Notch1 and Hes1 in brain tissues. Compared with the model group, the rats in miR-9 inhibitor group showed obviously improved learning and memory abilities, improved neuronal morphology of the brain, an obviously lower neuronal apoptosis rate in the brain, increased level of serum Bcl-2, decreased level of serum Bax, and obviously increased protein levels of Notch1 and Hes1 in brain tissues. In conclusion, miR-9 inhibitor can promote the neurological function recovery and inhibit the neuronal apoptosis of depression model rats through activating the Notch signaling pathway, suggesting that miR-9 can be an important therapeutic target for depression.

Identification of 14-3-3 epsilon as a regulator of the neural apoptotic pathway for chronic-stress-induced depression

“…Clinical and experimental studies indicate that multiple factors, such as dendritic retraction, suppressed neurogenesis, putative glial changes, and neuronal death, may contribute to the structural changes in the volume of the frontal cortex and hippocampus ( Czeh and Lucassen, 2007 ; Drzyzga et al., 2009 ; Lucassen et al., 2001 ). Although postmortem studies show little cellular death in the cortical area of MD patients, emerging animal studies suggest that elevated apoptotic signaling in MD may associate with pathogenesis of depression ( Fan et al., 2018 ; Salehpour et al., 2019 ; Xiao et al., 2020 ). In the present study, the Bcl-2 antagonist of death (Bad), a downstream proapoptotic factor, was also identified as one of the differentially expressed proteins by iTRAQ analysis.…”

Clinical Insights into MicroRNAs in Depression: Bridging Molecular Discoveries and Therapeutic Potential

“…A promising area of study involves the modulation of Notch 1, aimed at improving neural connectivity. Inhibition using miR-9 has been explored as a potential therapeutic strategy [ 142 , 143 , 144 ]. Furthermore, investigations using chronic unpredictable mild stress (CUMS) have revealed its role in triggering major depression through the downregulation of excitatory synapses, particularly affecting their presynaptic targets on GABAergic neurons in the nucleus accumbens [ 145 ].…”

Differential Learned Helplessness Phenotypes in Male and Female Rats: Exploring the Therapeutic Impact of Cannabidiol Treatment

“…Elevated miR-146 levels have been associated with TNF-α treatment [23] and correlated with depressive symptoms [17][18][19]. MiR-9 mediated depressive-like symptoms and its downregulation or inhibition decreased depressive-like behavior in UCMS mice, improved regeneration of hippocampal cells [21], and improved learning and memory in a water maze test [32]. MiR-9 also targets NF-κB1 and inhibits its expression, as was found in studies with immune disease patients [25][26]28].…”