New MicroRNAs as Candidates for Depression Therapy

Major depressive disorder (MDD) is a complex, common, and recurrent mental disorder (1). The current first-line treatment for MDD is selective serotonin reuptake inhibitors (SSRIs), which are antidepressant drugs that block serotonin reuptake.
Two microRNA (miRNAs) molecules namely miR-30b-5p and miR-101a-3p were found to be downregulated in the raphe nuclei (RN) of mice following chronic unpredictable stress (CUS) model for depression (2). These miRNAs were upregulated when the CUS treatment was performed along with application of the SSRI citalopram. The direct binding of these miRNAs to the 3’ UTR of Qki mRNA, and the subsequent effects on mRNA and protein levels of myelin basic protein (MBP), indicated involvement of these miRNAs in myelination ultrastructure processes in the RN, in response to CUS followed by SSRI treatment.
Based on our findings, we suggest a role for miR-30b-5p and miR-101a-3p, and their target gene Qki, in the mode of action of SSRI therapeutics.

MDD is among the leading global causes of disability, affecting more than 250 million people annually. Despite advancements in MDD treatment and management options, improvements have failed to meet patients’ desired outcomes. Consequently, MDD remains a severe and disabling disease with significant unmet needs for its treatment and management.

Our data indicates at a new mechanism and target proteins which underline the pathophysiology of MDD. This pathway may be modulated with miR-30b-5p and/or miR-101a-3p that are expected to upregulate MBP and possibly other genes involved in myelin homeostasis.
Expanding our knowledge on axon myelination deficits in MDD may open new venues for developing oligodendrocyte-targeted antidepressant therapeutics, possibly including miRNA mimics.

New therapy for MDD.

Publication and patent submitted. Further experiments are undergoing to expand our knowledge in miR’s role and mechanisms in MDD.

Provisional application submitted Aug, 2023

1. Sullivan et al., Aust. J. Pharm., 157, 2000
2. Israel-Elgali, J. Psych. Res., 166, 2023

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