Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum.
Pituitary adenylate cyclase activating polypeptide (PACAP) exhibits a protective effect against neural injury in vitro and in vivo. However, it has not been reported whether peripheral intravenous administration of PACAP could confer benefits in animal models of Parkinson's disease (PD). Furthermore, the underlying molecular mechanisms responsible for these effects are poorly understood. In the present experiments, we determined the effects and mechanism of action of intravenously administered PACAP27 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Our results indicate that intravenous injection of PACAP27 offers neuroprotective effects in the MPTP-induced PD mouse model which may not be directly associated with the expression levels of the monoamine transporters. However, this effect may be correlated with its ability to selectively regulate not only K(ATP) subunits, but D2 receptors in the striatum. Our findings suggest that the benefit of PACAP may accompany with changes not only in dopaminergic neurotransmission, but also in cholinergic neurotransmission that are relatively associated with the K(ATP) subunits and D2 receptors in the striatum.
Wang
Gang
G
Department of Neurology and Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Pan
Jing
J
Tan
Yu-Yan
YY
Sun
Xiao-Kang
XK
Zhang
Yong-Fang
YF
Zhou
Hai-Yan
HY
Ren
Ru-Jing
RJ
Wang
Xi-Jin
XJ
Chen
Sheng-Di
SD
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000502:physiology; D004563:Electrochemistry; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D054086:KATP Channels / Q000187:drug effects*; D020267:MPTP Poisoning / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects*; D018696:Neuroprotective Agents; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015306:Biogenic Monoamines; D007202:Indicators and Reagents; D054086:KATP Channels; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine