microRNAs and neuronal plasticity: from physiology to pathology.
31 mai 2016
Since 2005, my research activity has principally focused on the regulation of neuronal gene expression by microRNAs (miRNAs). miRNAs are small non-coding RNAs that inhibit protein translation by binding to the 3′ untranslated region (3′ UTR) of target mRNAs. miRNAs are abundant in the brain, with the challenge being to identify their roles and targets in specific neuronal functions.
We first demonstrated that miRNAs are key regulator of gene expression in the context of chronic neuropathic pain, with a tremendous therapeutic potential.
In a second study, we showed that miRNAs are also involved in cancer-related pain mechanisms and that miRNAs can be used as analgesic drugs.
In physiological conditions, miRNAs are also important regulators of synaptic protein expression. We recently showed that miRNAs regulate AMPA receptors expression during synaptic plasticity such as the homeostatic scaling paradigm.
Finally, my new project is based on the hypothesis that, in addition to classical synaptic communication, neurons are able to communicate through the exchange of RNAs shuttled between cells in extracellular vesicles called exosomes.
Letellier M, Elramah S, Mondin M, Soula A, Penn A, Choquet D, Landry M, Thoumine O, Favereaux A. miR-92a regulates expression of synaptic GluA1-containing AMPA receptors during homeostatic scaling. Nat Neurosci. 2014; 17(8):1040-2.
Elramah S, Landry M, Favereaux A. MicroRNAs regulate neuronal plasticity and are involved in pain mechanisms. Front Cell Neurosci. 2014; 8:31.
Kress M, Hüttenhofer A, Landry M, Kuner R, Favereaux A, Greenberg D, Bednarik J, Heppenstall P, Kronenberg F, Malcangio M, Rittner H, Uceyler N, Trajanoski Z, Mouritzen P, Birklein F, Sommer C, Soreq H. microRNAs in nociceptive circuits as predictors of future clinical applications. Front Mol Neurosci. 2013 Oct 17; 6:33.
Favereaux A, Thoumine O, Bouali-Benazzouz R, Roques V, Papon A, Abdel Salam S, Drutel G, Léger C, Calas A, Nagy F, Landry M. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. EMBO J. 2011; 30(18):3830-41.
Pr. Alain Trembleau
Pr. Valérie Fénelon
Dr. Eric Lingueglia
Dr Guillaume Van Niel
Dr. Olivier Thoumine
University of Bordeaux
Interdisciplinary Institute for NeuroScience – UMR 5297
Central mechanisms of pain sensitization