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Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease.
J Neuroendocrinol 2019; :e12782JN

Abstract

Gastrointestinal symptoms appear in Parkinson's disease patients many years before motor symptoms, suggesting the implication of dopaminergic neurones of the gut myenteric plexus. Inflammation is also known to be increased in PD. We previously reported neuroprotection with progesterone in the brain of mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and hypothesised that it also has neuroprotective and immunomodulatory activities in the gut. To test this hypothesis, we investigated progesterone administered to adult male C57BL/6 mice for 10 days and treated with MPTP on day 5. In an additional experiment, progesterone was administered for 5 days following MPTP treatment. Ilea were collected on day 10 of treatment and microdissected to isolate the myenteric plexus. Dopaminergic neurones were reduced by approximately 60% and pro-inflammatory macrophages were increased by approximately 50% in MPTP mice compared to intact controls. These changes were completely prevented by progesterone administered before and after MPTP treatment and were normalised by 8 mg kg-1 progesterone administered after MPTP. In the brain of MPTP mice, brain-derived neurotrophic peptide (BDNF) and glial fibrillary acidic protein (GFAP) were associated with progesterone neuroprotection. In the myenteric plexus, increased BDNF levels compared to controls were measured in MPTP mice treated with 8 mg kg-1 progesterone started post MPTP, whereas GFAP levels remained unchanged. In conclusion, the results obtained in the present study show neuroprotective and anti-inflammatory effects of progesterone in the myenteric plexus of MPTP mice that are similar to our previous findings in the brain. Progesterone is non-feminising and could be used for both men and women in the pre-symptomatic stages of the disease.

Authors+Show Affiliations

Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada. Faculty of Pharmacy, Laval University, Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada. Faculty of Pharmacy, Laval University, Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada. Faculty of Pharmacy, Laval University, Quebec, Canada.Axe Neurosciences, Centre de Recherche du CHU de Québec (Pavillon CHUL), Quebec, Canada. Faculty of Pharmacy, Laval University, Quebec, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31430407

Citation

Jarras, Hend, et al. "Neuroprotection and Immunomodulation of Progesterone in the Gut of a Mouse Model of Parkinson's Disease." Journal of Neuroendocrinology, 2019, pp. e12782.
Jarras H, Bourque M, Poirier AA, et al. Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease. J Neuroendocrinol. 2019.
Jarras, H., Bourque, M., Poirier, A. A., Morissette, M., Coulombe, K., Di Paolo, T., & Soulet, D. (2019). Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease. Journal of Neuroendocrinology, pp. e12782. doi:10.1111/jne.12782.
Jarras H, et al. Neuroprotection and Immunomodulation of Progesterone in the Gut of a Mouse Model of Parkinson's Disease. J Neuroendocrinol. 2019 Aug 20;e12782. PubMed PMID: 31430407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease. AU - Jarras,Hend, AU - Bourque,Mélanie, AU - Poirier,Andrée-Anne, AU - Morissette,Marc, AU - Coulombe,Katherine, AU - Di Paolo,Thérèse, AU - Soulet,Denis, Y1 - 2019/08/20/ PY - 2019/03/29/received PY - 2019/08/16/revised PY - 2019/08/16/accepted PY - 2019/8/21/pubmed PY - 2019/8/21/medline PY - 2019/8/21/entrez KW - MPTP KW - Parkinson's disease KW - gut KW - neuroprotection KW - progesterone SP - e12782 EP - e12782 JF - Journal of neuroendocrinology JO - J. Neuroendocrinol. N2 - Gastrointestinal symptoms appear in Parkinson's disease patients many years before motor symptoms, suggesting the implication of dopaminergic neurones of the gut myenteric plexus. Inflammation is also known to be increased in PD. We previously reported neuroprotection with progesterone in the brain of mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and hypothesised that it also has neuroprotective and immunomodulatory activities in the gut. To test this hypothesis, we investigated progesterone administered to adult male C57BL/6 mice for 10 days and treated with MPTP on day 5. In an additional experiment, progesterone was administered for 5 days following MPTP treatment. Ilea were collected on day 10 of treatment and microdissected to isolate the myenteric plexus. Dopaminergic neurones were reduced by approximately 60% and pro-inflammatory macrophages were increased by approximately 50% in MPTP mice compared to intact controls. These changes were completely prevented by progesterone administered before and after MPTP treatment and were normalised by 8 mg kg-1 progesterone administered after MPTP. In the brain of MPTP mice, brain-derived neurotrophic peptide (BDNF) and glial fibrillary acidic protein (GFAP) were associated with progesterone neuroprotection. In the myenteric plexus, increased BDNF levels compared to controls were measured in MPTP mice treated with 8 mg kg-1 progesterone started post MPTP, whereas GFAP levels remained unchanged. In conclusion, the results obtained in the present study show neuroprotective and anti-inflammatory effects of progesterone in the myenteric plexus of MPTP mice that are similar to our previous findings in the brain. Progesterone is non-feminising and could be used for both men and women in the pre-symptomatic stages of the disease. SN - 1365-2826 UR - https://www.unboundmedicine.com/medline/citation/31430407/Neuroprotection_and_immunomodulation_of_progesterone_in_the_gut_of_a_mouse_model_of_Parkinson's_disease L2 - https://doi.org/10.1111/jne.12782 DB - PRIME DP - Unbound Medicine ER -