Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, having a higher prevalence among men. Parkinsonian patients suffer from motor deficit, mostly characterize by muscle stiffness, tremors, slowing and imbalance. However, these disorders are generally preceded by non-motor symptoms like fatigue, anxiety, depression and gastrointestinal disorders such as constipation that can affect patients as far as 10 years prior to the onset of motor symptoms. It is moreover though that an insult or damage to the neuronal component surrounding the intestinal layer could be the origin of the gastrointestinal disorders and further brain insult via the propagation of neuronal metabolites by the vagus nerve.

This phenomenon is known as the Dr. Braak's hypothesis of the development of the Parkinson's disease. Using a parkinsonian mouse model, we already showed the neuroprotective impact of estrogen on the gut dopaminergic neurons. Moreover, we observe that the immune system could play a part in this protection. Hence, this project aim to evaluate the implication of estrogenic compounds in the protection of dopaminergic neurons and their immunomodulatory functions on the gut immune system. To do so, we will use multiple estrogenic treatments enabling us to reach different concentration of estrogen within the intestine. For now, our preliminary results show that the main effects of the estrogens in the gut are mainly mediated by a non-feminising receptor which is also not detrimentally affecting reproductive organs.