Melatonin ameliorates Alzheimer-like pathological changes and spatial memory retention impairment induced by calyculin A.
We have reported recently that inhibition of protein phosphatase (PP)-2A and PP-1 by calyculin A, a specific inhibitor of PP-2A and PP-1, induced Alzheimer-like hyperphosphorylation of tau and spatial memory retention impairment. In this study, we tested the in vivo effects of melatonin on these Alzheimer-like changes. We found that administration of melatonin intraperitoneally for 9 consecutive days before injection of calyculin A could prevent calyculin A-induced synaptophysin loss, memory retention deficits, as well as hyperphosphorylation of tau and neurofilaments. Furthermore, melatonin partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307 (Y307), a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde, a marker of oxidative stress, induced by calyculin A. These results suggest that melatonin could serve as a potential therapeutic agent for preventing Alzheimer-like pathological changes and behavioral abnormality via modulating the activity of PP-2A and oxidative stress.
Yang
Xifei
X
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Yang
Ying
Y
Fu
Zhengqi
Z
Li
Yin
Y
Feng
Jing
J
Luo
Jinzhuo
J
Zhang
Qiuyue
Q
Wang
Qun
Q
Tian
Qing
Q
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008387:Marine Toxins; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D010080:Oxazoles / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
D000975:Antioxidants; D008387:Marine Toxins; D010080:Oxazoles; D016875:tau Proteins; D008315:Malondialdehyde; C059041:calyculin A; D054648:Protein Phosphatase 2; D008550:Melatonin