EFFECTS OF (-)-SESAMIN ON MOTOR AND MEMORY DEFICITS IN AN MPTP-LESIONED MOUSE MODEL OF PARKINSON'S DISEASE TREATED WITH L-DOPA

The present study investigated the effects of (-)sesamin on motor and memory deficits in a 1-methyl-4-phe nyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP-lesioned (30 mg/kg/day, 5 days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25 mg/kg L-DOPA for 21 days. However, daily treatment with (-)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with L-DOPA (25 mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-D-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10 mg/kg L-DOPA for 21 days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving L-DOPA. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.