Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson's disease.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide, exerting different actions in the central and peripheral nervous systems. Among others, it has neurotrophic and neuroprotective effects. In the present study, we investigated the effects of PACAP 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 0.1 microg PACAP as a pretreatment. Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10 days postlesion when compared to animals receiving saline only. In only 1 day postlesion, by contrast, PACAP-treated rats showed no hypokinesia. Asymmetrical signs, such as turning, rearing and biased thigmotaxic scanning were observed in all lesioned animals 1 day postlesion. PACAP-treated animals, however, showed better recovery as they ceased to display asymmetrical signs 10 days later and showed markedly less apomorphine-induced rotations. Tyrosine-hydroxylase immunohistochemistry revealed that control animals had more than 95% loss of the dopaminergic cells in the ipsilateral substantia nigra, while PACAP-treated animals had only approximately 50% loss of dopaminergic cells. In summary, the present results show the neuroprotective effect of PACAP in 6-OHDA-induced lesion of substantia nigra, with less severe acute neurological symptoms and a more rapid amelioration of behavioral deficits.
Reglodi
Dóra
D
Department of Anatomy, Pécs University Medical Faculty, Neurohumoral Regulations Research Group of the Hungarian Academy of Sciences, Szigeti u 12, 7624 Pécs, Hungary. dora.reglodi@aok.pte.hu
Lubics
Andrea
A
Tamás
Andrea
A
Szalontay
Luca
L
Lengvári
István
I
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000633:toxicity; D001522:Behavior, Animal; D001526:Behavioral Symptoms / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000633:toxicity; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495403:Adcyap1 protein, rat; D018663:Adrenergic Agents; D018491:Dopamine Agonists; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine