Acetyl-L-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memory impairment in rats.
Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD). Protein phosphatases (PP) 2A plays a crucial role in AD-like lesions. Inhibition of PP2A through hippocampal injection of okadaic acid (OA) induces tau hyperphosphorylation and memory impairment of rats. By using this model, we explored in the present study the effects of acetyl-L-carnitine (ALCAR), a constituent of the inner mitochondrial membrane, on the memory retention, tau phosphorylation, and oxidative stress in rats. We found that pre-treatment of ALCAR (50 mg/d . rat, per os) for two weeks efficiently improved the OA-induced spatial memory retention impairment of the rats. ALCAR antagonized tau hyperphosphorylation at multiple AD sites and it abated the OA-induced PP2A inhibition and oxidative stress. Our study provides the first in vivo evidence that ALCAR can attenuate AD-like PP2A inhibition, tau hyperphosphorylation, and spatial memory deficit of the rats. It suggests that ALCAR may hold potential in AD treatment.
Yin
Yang-Yang
YY
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Liu
Hao
H
Cong
Xiao-Bin
XB
Liu
Zhao
Z
Wang
Qun
Q
Wang
Jian-Zhi
JZ
Zhu
Ling-Qiang
LQ
D000108:Acetylcarnitine / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019319:Okadaic Acid; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D018697:Nootropic Agents; D016875:tau Proteins; D019319:Okadaic Acid; D000108:Acetylcarnitine; D013482:Superoxide Dismutase; C514014:Ppp2ca protein, rat; D054648:Protein Phosphatase 2