Cyclosporin A attenuates degeneration of dopaminergic neurons induced by 6-hydroxydopamine in the mouse brain.
To reveal new therapeutic strategies for Parkinson's disease (PD), we investigated the protective effect of an immunosuppressant, cyclosporin A (CsA), against 6-hydroxydopamine (6-OHDA)-induced injury of nigrostriatal dopamine neurons in mice. Seven days after induction of 6-OHDA lesion, dopamine (DA) and homovanillic acid (HVA) in the striatum were depleted by 60 and 50%, respectively, and repeated high dose CsA (20 mg/kg) treatment significantly protected against these depletions. HVA and dihydroxyphenylacetic acid (DOPAC) in the substantia nigra were depleted by 40%, and CsA significantly increased HVA and DOPAC in 6-OHDA-lesioned mice. Furthermore, CsA increased the [DOPAC + HVA]/DA ratio in the substantia nigra, indicating that DA metabolism was stimulated by CsA in 6-OHDA-lesioned mice. These results suggest that CsA is beneficial in reducing 6-OHDA-induced injury of nigrostriatal DA neurons, indicating the therapeutic potential of immunosuppressants in PD.
Department of Neuroscience, Okayama University Medical School, Japan.
K
K
Matsuura
H
H
Kabuto
H
H
Makino
N
N
Ogawa
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017072:Neostriatum / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D016572:Cyclosporine; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid