Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease.

Publisher: Wiley & Sons Country of Publication: United States NLM ID: 8913461 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2826 (Electronic) Linking ISSN: 09538194 NLM ISO Abbreviation: J Neuroendocrinol Subsets: MEDLINE

Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-

Brain/*drug effects ; Dopaminergic Neurons/*drug effects ; Neuroprotective Agents/*therapeutic use ; Parkinsonian Disorders/*drug therapy ; Progesterone/*therapeutic use; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Brain/metabolism ; Brain/pathology ; Brain-Derived Neurotrophic Factor/metabolism ; Disease Models, Animal ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/pathology ; Glial Fibrillary Acidic Protein/metabolism ; Immunomodulation/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myenteric Plexus/drug effects ; Myenteric Plexus/metabolism ; Myenteric Plexus/pathology ; Neuroprotective Agents/pharmacology ; Parkinsonian Disorders/chemically induced ; Parkinsonian Disorders/metabolism ; Parkinsonian Disorders/pathology ; Progesterone/pharmacology

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.
(© 2019 British Society for Neuroendocrinology.)

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CFI-25631 International Canadian Foundation for Innovation; MOP-275325 International Canadian Institute of Health Research

Keywords: MPTP; Parkinson's disease; gut; neuroprotection; progesterone

0 (Brain-Derived Neurotrophic Factor)
0 (Glial Fibrillary Acidic Protein)
0 (Neuroprotective Agents)
4G7DS2Q64Y (Progesterone)
9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

Date Created: 20190821 Date Completed: 20210526 Latest Revision: 20210526

20240829

10.1111/jne.12782

31430407