| Description |
Tourette syndrome (TS) is a neurodevelopmental condition with a marked male predominance (M: F= 3:1), characterized by multiple motor and one or more vocal tics for more than one year and beginning before the age of 18 (Robertson, 2019). Our understanding of TS pathophysiology remains limited; as a result, available pharmacotherapies remain only partially effective and lead to numerous side effects. This project seeks to use animal models of TS to evaluate whether the steroids dehydroepiandrosterone (DHEA) play a role in the pathophysiology of TS by exacerbating or triggering tics. Two main premises suggest the implication of DHEA in TS: - The age of onset of tics, 6-8 years (Parker, 1991), corresponds to adrenarche, the first stage of sexual differentiation to trigger the progression of puberty. This stage is characterized by an increased synthesis of DHEA (Jameson & Finlayson, 2010); - Children with chronic tic disorders have been shown to display higher circulating DHEA-S levels than age-matched healthy controls (Erbay et al., 2016). To study the implication of DHEA in TS, we used the mouse model of striatal cholinergic interneuron (CIN) depletion. This model is based on the partial loss of CIN in the dorsal striatum, one of the best-characterized pathophysiological features of TS (Kalanithi et al., 2005; Kataoka et al., 2010). Mice subjected to early-life striatal CIN depletion exhibit TS-relevant deficits, such as tic-like stereotypies. Based on these premises, we hypothesized that DHEA may increase tic-like stereotypies in CIN-depleted mice (compared with their intact controls). In line with our hypothesis, we found that DHEA, but not its steroid precursors and metabolites, increases the number of tic-like stereotypies in CIN-depleted mice. The results of our study point to DHEA as a potential exacerbating factor for tics and suggest that DHEA may be the mechanism whereby the clinical onset corresponds to adrenarche. If these results are confirmed by further clinical observations, they may lead to the development of novel therapies for TS. |
