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Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice.
Eur Neuropsychopharmacol. 2005 Jan; 15(1):57-67.EN

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).

Authors+Show Affiliations

Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15572274

Citation

Kurosaki, Rumiko, et al. "Effect of Angiotensin-converting Enzyme Inhibitor Perindopril On Interneurons in MPTP-treated Mice." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 15, no. 1, 2005, pp. 57-67.
Kurosaki R, Muramatsu Y, Kato H, et al. Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice. Eur Neuropsychopharmacol. 2005;15(1):57-67.
Kurosaki, R., Muramatsu, Y., Kato, H., Watanabe, Y., Imai, Y., Itoyama, Y., & Araki, T. (2005). Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 15(1), 57-67.
Kurosaki R, et al. Effect of Angiotensin-converting Enzyme Inhibitor Perindopril On Interneurons in MPTP-treated Mice. Eur Neuropsychopharmacol. 2005;15(1):57-67. PubMed PMID: 15572274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice. AU - Kurosaki,Rumiko, AU - Muramatsu,Yasuko, AU - Kato,Hiroyuki, AU - Watanabe,Yu, AU - Imai,Yutaka, AU - Itoyama,Yasuto, AU - Araki,Tsutomu, PY - 2004/03/30/received PY - 2004/05/11/accepted PY - 2004/12/2/pubmed PY - 2005/3/30/medline PY - 2004/12/2/entrez SP - 57 EP - 67 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 15 IS - 1 N2 - 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). SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/15572274/Effect_of_angiotensin_converting_enzyme_inhibitor_perindopril_on_interneurons_in_MPTP_treated_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924977X04000884 DB - PRIME DP - Unbound Medicine ER -