Cerebral alterations in a MPTP-mouse model of Parkinson's disease--an immunocytochemical study.
We investigated the immunohistochemical alterations of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), tyrosine hydroxylase (TH), microtubule-associated protein 2a,b (MAP 2), glial fibrillary acidic protein (GFAP), parvalbumin (PV), and dopamine transporter (DAT) in the striatum and substantia nigra following the application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. TH-, MAP 2- and DAT-immunoreactive cells were decreased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment, as well as the reduction of the striatal dopamine, DOPAC and HVA content. The number of GFAP-immunoreactive astrocytes increased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment. Striatal nNOS-immunoreactive cells were unchanged in MPTP-treated mice. In the substantia nigra, intense immunoreactivity of nNOS-positive cells increased 5 hr after MPTP treatment. Thereafter, the immunoreactivity of nNOS-positive cells decreased gradually from 1 day up to 7 days after MPTP treatment. eNOS-immunopositive cells were unchanged in the striatum and substantia nigra. These results demonstrate that nNOS may play a key role in the development of MPTP neurotoxicity. Our findings also indicate that MPTP can cause the functional damage of interneurons in the substantia nigra, but not in the striatum.
Muramatsu
Y
Y
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan.
Kurosaki
R
R
Watanabe
H
H
Michimata
M
M
Matsubara
M
M
Imai
Y
Y
Araki
T
T
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000633:toxicity; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020267:MPTP Poisoning; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; C493215:Slc6a3 protein, mouse; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D014446:Tyrosine 3-Monooxygenase