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

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.

[1]  X-m Zhang,et al.  Silence of MiR-9 protects depression mice through Notch signaling pathway. , 2019, European review for medical and pharmacological sciences.

[2]  Fang Li,et al.  miR-9 stimulation enhances the differentiation of neural stem cells with zoanthamine by regulating Notch signaling. , 2019, American journal of translational research.

[3]  X. Yi,et al.  A study on related factors of hemodynamic depression in carotid artery stenting. , 2018, European review for medical and pharmacological sciences.

[4]  C. Hammen,et al.  Risk Factors for Depression: An Autobiographical Review. , 2018, Annual review of clinical psychology.

[5]  S. Mousavi,et al.  MicroRNAs and exosomes in depression: Potential diagnostic biomarkers , 2018, Journal of cellular biochemistry.

[6]  G. Turecki,et al.  Major depression and its treatment: microRNAs as peripheral biomarkers of diagnosis and treatment response , 2018, Current opinion in psychiatry.

[7]  M. Fang,et al.  Prospective Role of MicroRNAs in Depression. , 2017, Current medicinal chemistry.

[8]  M. Krasnow,et al.  MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis. , 2017, Cell reports.

[9]  M. Du,et al.  Effects of the Notch signalling pathway on hyperoxia-induced immature brain damage in newborn mice , 2017, Neuroscience Letters.

[10]  T. Rahim,et al.  Comparison of depression symptoms between primary depression and secondary-to-schizophrenia depression , 2017, International journal of psychiatry in clinical practice.

[11]  M. S. Cepeda,et al.  Microbiome-Gut-Brain Axis: Probiotics and Their Association With Depression. , 2017, The Journal of neuropsychiatry and clinical neurosciences.

[12]  Qinwen Wang,et al.  SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1–42 into hippocampus of mice , 2017, Metabolic Brain Disease.

[13]  F. Guillemot,et al.  A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States , 2016, Cell reports.

[14]  Daehyun Baek,et al.  The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory , 2016, The Journal of Neuroscience.

[15]  P. Brambilla,et al.  Brain Structural Effects of Antidepressant Treatment in Major Depression , 2015, Current neuropharmacology.

[16]  Kerri Smith,et al.  Mental health: A world of depression , 2014, Nature.

[17]  E. Anthes Depression: A change of mind , 2014, Nature.

[18]  K. Deisseroth,et al.  Depression: The best way forward , 2014, Nature.

[19]  L. Bally-Cuif,et al.  Cellular Neuroscience , 2022 .

[20]  Pasko Rakic,et al.  Not(ch) just development: Notch signalling in the adult brain , 2011, Nature Reviews Neuroscience.