Dr. Rixing Lin, McGill University
Lin R, Kos A, Lopez JP, Dine J, Fiori LM, Yang J, Ben-Efraim Y, Aouabed Z, Ibrahim P, Mitsuhashi H, Wong TP, Ibrahim EC, Belzung C, Blier P, Farzan F, Frey BN, Lam RW, Milev R, Muller DJ, Parikh SV, Soares C, Uher R, Nagy C, Mechawar N, Foster JA, Kennedy SH, Chen A, Turecki G. SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants. Elife. 2023 Jul 11;12:e85316. doi: 10.7554/eLife.85316.
PMID: 37432876; PMCID: PMC10335830.
A small RNA molecule mediates antidepressant response
Antidepressants are the first-line treatment for major depressive disorder (MDD). While most currently available antidepressants act by targeting serotonin receptors the exact mechanisms by which they effect mood changes and improvements in depression symptoms remain unknown. In a new study, Dr. Rixing Lin and colleagues uncover a previously unrecognized molecular link between conventional serotonin-targeting antidepressants and the fast-acting effects associated with the glutamatergic system in the brain.
This article specifically explores the role of SNORD90, a small nucleolar RNA (snoRNA), and shows it can facilitate glutamatergic signaling following treatment with antidepressants targeting serotonin signaling. The researchers provide extensive data from human plasma and post-mortem brain, mouse brain, and cultured cells to enrich our understanding of the intricate molecular mechanisms that underlie the effects of antidepressants.
A groundbreaking revelation emerges as SNORD90, whose function was previously unknown, influences the expression of a protein called neuregulin 3, through a process involving RNA modifications, ultimately resulting in heightened activity within the glutamatergic system. This groundbreaking research uncovers an unprecedented molecular connection between traditional antidepressant treatments and the glutamatergic system.
These discoveries hold promise for advancing our understanding of MDD treatment, enhancing our basic understanding of snoRNAs, and paving the way for innovative therapeutic approaches in the future.
About Dr. Rixing Lin
Dr. Rixing Lin completed his PhD under the supervision of Dr. Gustavo Turecki at McGill University, where the work described here was conducted. Dr. Rixing Lin was involved in the conception, conducting and coordination of all aspects of the research, data interpretation, and preparation of the manuscript. Currently, Dr. Rixing Lin is a C.V. Starr Postdoctoral Fellow at Princeton University in the lab of Dr. Catherine Peña and hopes to start his own independent lab in the future.
Sources of funding
Major support for this study was provided by the Canadian Institutes of Health Research, Fonds de recherche du Québec -Santé, the Ontario Brain Institute and German Ministry of Science and Education.
