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 provided the first in vivo evidence that ALCAR could attenuate AD-like PP2A inhibition, tau hyperphosphorylation, and spatial memory deficit of the rats. It suggests that ALCAR may be potential in AD treatment.
Yin YY, Liu H, Cong XB, Liu Z, Wang Q, Wang JZ, Zhu LQ. Acetyl-L-Carnitine Attenuates Okadaic Acid Induced Tau Hyperphosphorylation and Spatial Memory Impairment in Rats. J Alzheimers Dis. 2009 November Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.