Morphological and functional effects of PACAP in 6-hydroxydopamine-induced lesion of the substantia nigra in rats.
Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system, including neuroprotective effects. In the present study, we investigated the effects of different doses of PACAP on the functional and morphological outcome in a rat model of Parkinson's disease. Rats were given unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra. PACAP-treated animals received 1, 0.1 or 0.01 microg PACAP as a pretreatment. Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10 days post-lesion when compared to normal animals or those receiving saline only. PACAP treatment resulted in less severe acute hypokinesia, and complete recovery by 10 days. Asymmetrical signs were observed in all lesioned animals 1 day post-lesion. PACAP-treated animals, however, showed better recovery as they ceased to display asymmetrical signs 10 days later and showed markedly less apomorphine-induced rotations. Best behavioral outcome was observed in animals treated with 0.1 microg PACAP. Tyrosine-hydroxylase (TH) immunohistochemistry revealed increased number of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area in all PACAP-treated rats in contrast to the severe cell loss in control animals. These results indicate that PACAP may be a promising therapeutic agent in Parkinson's disease.
Reglodi
Dóra
D
Department of Anatomy, Pécs University Medical Faculty and Neurohumoral Regulations Research Group of the Hungarian Academy of Sciences, Szigeti u 12, 7624 Pécs, Hungary. dora.reglodi@aok.pte.hu
Tamás
Andrea
A
Lubics
Andrea
A
Szalontay
Luca
L
Lengvári
István
I
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology / Q000523:psychology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495403:Adcyap1 protein, rat; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase