title: Pituitary adenylate cyclase-activating polypeptide (PACAP) has a neuroprotective function in dopamine-based neurodegeneration in rat and snail parkinsonian models.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA)-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7 protein concentrations were measured before and after PACAP treatment in both models. Locomotion and feeding activity were decreased in rotenone-treated snails, which corresponded well to findings obtained in 6-OHDA-induced rat experiments. PACAP was able to prevent the behavioural malfunctions caused by the toxins. Monoamine levels decreased in both models and the decreased DA level induced by toxins was attenuated by ∼50% in the PACAP-treated animals. In contrast, PACAP had no effect on the decreased serotonin (5HT) levels. S-COMT metabolic enzyme was also reduced but a protective effect of PACAP was not observed in either of the models. Following toxin treatment, a significant increase in MB-COMT was observed in both models and was restored to normal levels by PACAP. A decrease in PARK7 was also observed in both toxin-induced models; however, PACAP had a beneficial effect only on 6-OHDA-treated animals. The neuroprotective effect of PACAP in different animal models of Parkinson's disease is thus well correlated with neurotransmitter, enzyme and protein levels. The models successfully mimic several, but not all etiological properties of the disease, allowing us to study the mechanisms of neurodegeneration as well as testing new drugs. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models offer an alternative method for investigation of the molecular mechanisms of neuroprotective agents, including PACAP.
authors.affiliation: MTA-ÖK BLI NAP_B Adaptive Neuroethology, Department of Experimental Zoology, Balaton Limnological Institute, MTA-CER, 8237 Tihany, Hungary.|Department of Analytical Biochemistry, Institute of Biochemistry and Medical Chemistry, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Gabor
authors.identifier: 0000-0001-5524-1424
authors.initials: G
authors.lastname: Maasz
authors.affiliation: MTA-ÖK BLI NAP_B Adaptive Neuroethology, Department of Experimental Zoology, Balaton Limnological Institute, MTA-CER, 8237 Tihany, Hungary.
authors.forename: Zita
authors.identifier: 0000-0001-9446-4874
authors.initials: Z
authors.lastname: Zrinyi
authors.affiliation: Department of Anatomy, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Dora
authors.identifier: 0000-0001-5481-5529
authors.initials: D
authors.lastname: Reglodi
authors.affiliation: Department of Analytical Biochemistry, Institute of Biochemistry and Medical Chemistry, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Dora
authors.identifier: 0000-0002-3183-8178
authors.initials: D
authors.lastname: Petrovics
authors.affiliation: Department of Anatomy, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Adam
authors.identifier: 0000-0001-9577-9317
authors.initials: A
authors.lastname: Rivnyak
authors.affiliation: Department of Experimental Zoology, Balaton Limnological Institute, MTA-CER, 8237 Tihany, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kiss
authors.affiliation: Department of Anatomy, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Adel
authors.initials: A
authors.lastname: Jungling
authors.affiliation: Department of Anatomy, University of Pecs, 7624 Pecs, Hungary.
authors.forename: Andrea
authors.identifier: 0000-0002-0086-7566
authors.initials: A
authors.lastname: Tamas
authors.affiliation: MTA-ÖK BLI NAP_B Adaptive Neuroethology, Department of Experimental Zoology, Balaton Limnological Institute, MTA-CER, 8237 Tihany, Hungary pirger.zsolt@okologia.mta.hu.
authors.forename: Zsolt
authors.identifier: 0000-0001-9039-6966
authors.initials: Z
authors.lastname: Pirger
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine; D005247:Feeding Behavior; D008124:Locomotion; D013058:Mass Spectrometry; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology / Q000627:therapeutic use*; D000071617:Protein Deglycase DJ-1 / Q000378:metabolism; D040901:Proteomics; D017208:Rats, Wistar; D012402:Rotenone; D012701:Serotonin / Q000378:metabolism; D012908:Snails; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012402:Rotenone; D012701:Serotonin; D016627:Oxidopamine; D000071617:Protein Deglycase DJ-1; D004298:Dopamine
keywords: 6-OHDA; DJ-1; Dopamine; PACAP; PARK7; PD models; Rotenone