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Updated: Aug 20, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice
Rumiko Kurosaki1, Yasuko Muramatsu, Hiroyuki Kato
1Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan.
Abstract:
We examined the effects of perindopril on the dopaminergic system in mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. The mice received four intraperitoneal injections of MPTP at 1-h intervals. Administration of perindopril showed dose-dependent neuroprotective effects against striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion 3 days after MPTP treatment. Our immunohistochemical study showed that MPTP can severe damage in tyrosine hydroxylase (TH)-immunoreactive neurons after MPTP treatment. The administration of perindopril significantly attenuated MPTP-induced substantia nigra and striatal damage. The present study also showed that the immunoreactivity of parvalbumin (PV)- or neuronal nitric oxide synthase (nNOS)-positive cells in the substantia nigra was decreased 7 days after MPTP treatment, whereas no significant changes were observed in these cells of the striatum throughout the experiments. The administration of perindopril significantly attenuated MPTP-induced decrease of the PV- or nNOS-immunoreactivity in the nigral cells. In double-labeled immunostaining with anti-PV and anti-nNOS antibody, PV-immunoreactive cell bodies and fibers were not double-labeled for nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra after MPTP treatment. Furthermore, PV- or nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra were not double-labeled for TH-immunoreactive cell bodies and fibers. These results demonstrate that the ACE inhibitor perindopril has a dose-dependent protective effect against MPTP-induced striatal dopamine, DOPAC and HVA depletion in mice. The present study also demonstrates that perindopril is effective against MPTP-induced degeneration of the nigral neurons and interneurons. Furthermore, our immunohistochemical study suggests that PV-immunoreactive cells and nNOS-immunoreactive cells are different interneurons in both the striatum and substantia nigra. Thus, our results provide further evidence that the ACE inhibitor perindopril may offer a novel therapeutic strategy for Parkinson's disease (PD).
Insights
Perindopril, an ACE inhibitor, demonstrated neuroprotective effects against MPTP-induced damage in mice, preserving dopamine levels and mitigating neuronal degeneration. This suggests perindopril as a potential therapeutic for Parkinson's disease.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons.
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to model PD in mice.
- The dopaminergic system, particularly the substantia nigra and striatum, is critically affected in PD.
Purpose of the Study:
- To investigate the neuroprotective effects of perindopril on the dopaminergic system in a mouse model of Parkinson's disease.
- To evaluate the impact of perindopril on MPTP-induced depletion of dopamine and its metabolites.
- To assess the effect of perindopril on neuronal damage in the substantia nigra and striatum.
Main Methods:
- Mice were treated with MPTP to induce Parkinsonian pathology.
- Perindopril was administered at varying doses to assess dose-dependent effects.
- Immunohistochemistry was employed to evaluate tyrosine hydroxylase (TH), parvalbumin (PV), and neuronal nitric oxide synthase (nNOS) immunoreactivity.
Main Results:
- Perindopril showed dose-dependent neuroprotection against MPTP-induced depletion of striatal dopamine, DOPAC, and HVA.
- Perindopril significantly attenuated MPTP-induced damage to TH-immunoreactive neurons in the substantia nigra and striatum.
- Perindopril protected against the MPTP-induced decrease in PV- and nNOS-immunoreactivity in nigral cells, suggesting protection of interneurons.
Conclusions:
- Perindopril exhibits significant neuroprotective properties against MPTP-induced neurodegeneration.
- The findings support the potential of perindopril as a novel therapeutic strategy for Parkinson's disease.
- Perindopril may protect nigral neurons and interneurons, offering a multifaceted approach to PD treatment.
