Dopaminergic transplants suppress l-DOPA-induced Fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease

• Published in: Brain research Vol. 727; no. 1; pp. 205 - 211
• Main Authors: Ishida, Yasushi, Kuwahara, Itsumi, Todaka, Kazunari, Hashiguchi, Hiroyuki, Nishimori, Toshikazu, Mitsuyama, Yoshio
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 15-07-1996; Amsterdam Elsevier; New York, NY
• Subjects: 6-Hydroxydopamine; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Brain Tissue Transplantation; Caudate Nucleus - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dizocilpine Maleate - pharmacology; Dopamine - metabolism; Female; Fetal Tissue Transplantation; Fos protein; l-DOPA; Levodopa - pharmacology; Medical sciences; Mesencephalon - transplantation; Methamphetamine - pharmacology; MK-801: Dopaminergic transplant; Motor Activity - drug effects; Neuropharmacology; NMDA receptor; Oxidopamine; Parkinson Disease, Secondary - metabolism; Parkinson Disease, Secondary - physiopathology; Parkinson Disease, Secondary - surgery; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-fos - biosynthesis; Putamen - metabolism; Rat; Rats; Rats, Wistar; Striatum; Tyrosine 3-Monooxygenase - biosynthesis; Striatum; Fos protein; Rat; 6-Hydroxydopamine; MK-801: Dopaminergic transplant; l-DOPA; NMDA receptor; Animal model; Nervous system diseases; Dopamine; Rodentia; Central nervous system; Parkinson disease; Basal ganglion; Corpus striatum; Transplantation; Catecholamine; Gene expression; Antiparkinson agent; Cerebral disorder; Vertebrata; Mammalia; Treatment; Animal; Central nervous system disease; Neurotransmitter; Degenerative disease; Dopa; Brain (vertebrata); Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(96)00381-2

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.