Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration developed in two parkinsonian models

Abstract

It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents 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. The 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 5HT levels. The S-COMT metabolic enzyme was reduced in both models; however, the protective effect of PACAP was not present in any of the models. Following the toxin treatments a significant increase in the MB-COMT level was observed in both models and the increased MB-COMT level was successfully restored by PACAP. The decrease of PARK7/DJ-1 protein content was also observed in both toxin-induced models; however, PACAP had beneficial effect only on 6-OHDA-treated animals. We conclude that the neuroprotective effect of PACAP in different animal models of Parkinson's disease is well correlated with neurotransmitter, enzyme and protein levels. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models successfully mimic several, but not all etiological properties of the disease. Their use allows us to study both the mechanisms of neurodegeneration as well as to test new drugs. Appropriate selection of the models might offer an alternative way for investigating the molecular mechanisms of neuroprotective agents including PACAP.