Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson's disease model in mice

Abstract

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and protects neurons from various injuries. Our previous study has shown that Trx-1 overexpression attenuates movement disorder in PD. However, whether Trx-1 ameliorates cognitive deficits in PD is still unknown. In the present study, we investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice. We demonstrated that deficits in learning and memory were induced by MPTP in mice through the elevated plus-maze test. We found that the retention transfer latency time was shorten, escape latency was decreased and the number of platform crossings was increased in the Morris water maze (MWM) in Trx-1 transgenic (TG) mice when compared with wild type mice. The expressions of tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) were decreased by MPTP, which were restored in Trx-1 TG mice. The expression of N-methyl-D-aspartate receptor 2B subunit (NR2B), the levels of phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cAMP-response element binding protein (CREB) in the hippocampus were decreased by MPTP, which were reversed in Trx-1 TG mice. These results suggest that Trx-1 ameliorates learning and memory deficits in MPTP-induced PD model in mice via modulating the D1R and the NMDAR-ERK1/2-CREB pathway. Trx-1 may be a therapy target for learning and memory deficits in PD.