Thesis defense – Anaïs Marie

Venue : CGFB and on Zooom

https://bordeaux-inp-fr.zoom.us/j/82563864675?pwd=aEZoR2VZeVhMNUNscUxkNTJWajJUdz09

ID de réunion : 825 6386 4675

Code secret : 138792

Role of vitamin A in the maintenance of the striatum and the nigro-striatal pathway integrity and in the context of Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease characterized by the degeneration of dopaminergic neurons from the substantia nigra pars compacta (SNc) leading to the development of motor symptoms. Projections of dopaminergic neurons from the SNc to the striatum constitute the nigro-striatal pathway whose activity in the basal ganglia network is essential for the control of voluntary movement. Several clinical and preclinical studies suggest an involvement of vitamin A and it signaling pathway mediated by its active metabolite, retinoic acid (RA), in the development and maintenance of the integrity of the nigro-striatal pathway. However, with aging or deficient dietary intake, a collapse of retinoid signaling is observed, which may contribute to the etiology of PD. Current treatments for PD do not prevent neurodegeneration and are associated to severe long-term side effects, highlighting the need to develop alternative therapeutics.

In that context, the general objective of this thesis was to further understand the involvement of retinoid signaling in the functional homeostasis of the nigro-striatal pathway in adulthood, and to determine the potential benefit of vitamin A nutritional supplementation to delay the progression of PD.

Results of a first study in an adult rat model of PD with intrastriatal injection of 6-hydroxydopamine (6-OHDA) have revealed a beneficial effect of nutritional vitamin A supplementation on striatal function and an improvement of 6-OHDA-induced motor deficits. However, analyses did not reveal a strong effect of dietary vitamin A intake on the dopaminergic system. Furthermore, the impact of vitamin A bioavailability on striatal neuromodulation in adult rats has been investigated with diets containing different amount of vitamin A (sub-deficient, sufficient or enriched). Here, vitamin A sub-deficiency initiated in adulthood constituted an original approach to model alteration of retinoid signaling excluding developmental effects. Results reveal an involvement of retinoid signaling in the maintenance of the integrity of cholinergic system and the architecture of the striatum in adulthood. Additionally, results suggest a differential sensitivity of the dopaminergic system to vitamin A signaling between adulthood and the developmental period.

In conclusion, this thesis work demonstrates the importance of retinoid signaling to maintain physiological activity of the striatum and the nigro-striatal pathway in adulthood. As part of personalized medicine, nutritional supplementation with vitamin A could improve the management of patients and the prevention of PD.

Key words: vitamin A, nutrition, nigro-striatal pathway, dopamine, Parkinson’s disease, neuromodulation, adulthood

Publications

Preventive vitamin A supplementation improves striatal function in 6-hydroxydopamine hemiparkinsonian rats.
Marie, A., Leroy, J., Darricau, M., Alfos, S., De Smedt-Peyrusse, V., Richard, E., Vancassel, S., Bosch-Bouju, C.
Accepté dans Frontiers in Nutrition.

Review :  Role and Mechanism of Vitamin A Metabolism in the Pathophysiology of Parkinson’s Disease.
Marie et al., 2021.
DOI : 10.3233/JPD-212671

Preventive vitamin A supplementation improves striatal function in 6-hydroxydopamine hemiparkinsonian rats.
Marie et al
Soumis à Neurobiology of disease

Jury

Rapporteur : Sébastien Carnicella, CR, Grenoble, HDR
Rapporteur : Wojciech Krezel, Pr, Strasbourg, HDR
Examinateur : Agnes Nadjar, Prv, Bdx, HDR, présidente du jury
Examinateur : Catherine Féart, CR, Bdx, HDR
Examinateur : Emmanuel Moyse; Pr, Tours, HDR