Dopaminergic transplants suppress L-DOPA-induced Fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease.
We examined the effects of MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and fetal ventral mesencephalic (VM) transplants on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced Fos protein expression in the dopamine (DA)-depleted striatum. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were produced in young adult female rats and grafting was performed 3 weeks later. Methamphetamine-induced rotational behavior recovered significantly on the 4th week after grafting. Immunohistochemical examinations of c-Fos and tyrosine hydroxylase (TH) were performed 3-4 months after grafting. L-DOPA (100 mg/kg, i.p.) markedly induced Fos-like immunoreactivity (FLI) in the DA-depleted striatum. Pretreatment with a large dose of MK-801 (3-4.5 mg/kg, i.p.) dose-dependently suppressed L-DOPA-induced FLI in the striatum. The stimulatory effect of L-DOPA on c-Fos expression observed within the lesioned striatum was suppressed by fetal VM transplants. It seemed that the graft-induced effect on FLI extended over a considerably larger area than that covered by the graft-derived TH-immunoreactive innervation. Taken together, these findings suggest that glutamatergic modulation is involved in the L-DOPA-induced c-Fos expression in the denervated striatum which is normalized by fetal VM transplants. It also seems likely that VM grafts suppress the L-DOPA-induced expression of transcriptional factors which might be involved in the mechanisms underlying various side effects of chronic L-DOPA therapy.
Ishida
Y
Y
Department of Psychiatry, Miyazaki Medical College, Japan. ishiday@post.miyazaki-med.ac.jp
Kuwahara
I
I
Todaka
K
K
Hashiguchi
H
H
Nishimori
T
T
Mitsuyama
Y
Y
D000818:Animals; D016380:Brain Tissue Transplantation; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D007980:Levodopa / Q000494:pharmacology*; D008636:Mesencephalon / Q000637:transplantation*; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011699:Putamen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; D007980:Levodopa; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine