Oxidative stress and microglial activation in substantia nigra following striatal MPP+.
The present study aims to study sequential alterations occurring in both dopaminergic neurons and microglia in substantia nigra (SN) following intrastriatal injection of 1-methyl-4-phenylpridium ion (MPP+) in rats. Heme oxygenase-1 (HO-1), a marker of oxidative stress, first appeared in dopaminergic neurons in SN at 1 day post-lesion. Subsequently, microglia in SN exhibited morphological changes indicative of activation. At 7 days post-lesion, those findings increased severity and 7a significant reduction in the number of dopaminergic neurons was observed. The present finding suggests that extensive oxidative stress and secondary-induced neuroinflammation play a relevant role in MPP(+)-induced retrograde dopaminergic neuron degeneration. We hope that this model will be useful in developing a disease modifying therapy of Parkinson's disease.
Miwa
Hideto
H
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jph
Kubo
Tomomi
T
Morita
Shuhei
S
Nakanishi
Ichiro
I
Kondo
Tomoyoshi
T
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D015655:1-Methyl-4-phenylpyridinium