Ropinirole protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice via anti-apoptotic mechanism.
Ropinirole is a pharmacologically active agent used in the treatment of Parkinson's disease (PD) that directly acts on dopamine receptors. Recent studies reported that ropinirole has neuroprotective potential. However, there have been no detailed studies on apoptosis. Here we demonstrated the protective effects of ropinirole against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Unlike previous studies, we focused on apoptotic pathways. To confirm the protective effect of ropinirole, we conducted behavioral tests and tyrosine hydroxylase (TH)-immunohistochemistry. In the pole test and the rotarod test, commonly used behavioral tests in the mouse model of PD, ropinirole treatment (0.5, 1, or 2 mg/kg) maintained movement ability against MPTP-induced changes in motor coordination and postural balance, and bradykinesia. Our histological analyses illustrated that ropinirole significantly reduced MPTP-induced dopaminergic neuron damage in both the substantia nigra pars compacta (SNpc) and the striatum. In addition, we performed Western blot or kit analysis to measure apoptosis-related protein levels in the SNpc. Ropinirole increased the Bcl-2/Bax ratio, transcription factor A, and nuclear respiratory factor 1 and inhibited cytosolic cytochrome c release and caspase-3 activity, indicating that ropinirole inhibited the apoptotic cascade. These results suggest that ropinirole has neuroprotective effects in a mouse model of PD by inhibiting apoptosis.
Department of Life and Nanopharmaceutical Science, and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Gunhyuk
G
Park
Young-Joon
YJ
Park
Hyun Ok
HO
Yang
Myung Sook
MS
Oh
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006609:High Mobility Group Proteins / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000978:Antiparkinson Agents; C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D018491:Dopamine Agonists; D006609:High Mobility Group Proteins; D007211:Indoles; D018696:Neuroprotective Agents; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D019253:Proto-Oncogene Proteins c-bcl-2; C081930:Tfam protein, mouse; D051028:bcl-2-Associated X Protein; C046649:ropinirole; D045304:Cytochromes c; C505409:Casp3 protein, mouse; D053148:Caspase 3