title: Effects of (-)-sesamin on motor and memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with l-DOPA.
abstract: The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/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 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/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.
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: T T
authors: TT
authors: Zhao
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: K S
authors: KS
authors: Shin
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: K S
authors: KS
authors: Kim
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: H J
authors: HJ
authors: Park
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: H J
authors: HJ
authors: Kim
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea.
authors: K E
authors: KE
authors: Lee
authors: Department of Pharmacy and Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, 1, Chungdae-ro, Seowon-gu, Cheongju 28644, Republic of Korea. Electronic address: myklee@chungbuk.ac.kr.
authors: M K
authors: MK
authors: Lee
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000737:chemistry / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D012333:RNA, Messenger / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000978:Antiparkinson Agents; D004149:Dioxoles; D017705:Lignans; D018697:Nootropic Agents; D012333:RNA, Messenger; D007980:Levodopa; C054125:sesamin; D004298:Dopamine
keywords: (−)-sesamin; MPTP lesion; Parkinson’s disease; l-DOPA; motor and memory deficits