Induction of synaptic plasticity by rehabilitation environment in Parkinson’s disease with α-synucleinopathy

Abstract

Parkinson’s dis ease (PD) is a neurodegenerative disease characterized by motor symptoms with accompanying non-motor symptoms such as olfactory loss, cognitive decline, depression and anxiety, which frequently appear in the early stage of the disease, including the pre-motor phase. Environmental enrichment (EE) which provides a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral functions. However, there is no research on the effect of EE on non-motor symptoms in human A53T overexpressing transgenic mice. This study investigated the influence of an EE on change of synaptic plasticity in striatum and nucleus accumbens during the initial phase of PD. Eight-month-old human A53T overexpressing mice were randomly allocated to EE or standard conditions (SC) for two months. EE significantly ameliorated hyperactivity and anxiety in A53T mice which was demonstrated by an open field test. Dopaminergic neurons in the substantia nigra pars compata (SNpc) and ventral tegmental area (VTA) had not degenerated at 10 months of age. Dopaminergic nerve terminals of the striatum significantly decreased about 20% in A53T SC and A53T EE compared to wild-type (WT). Those of the nucleus accumbens significantly decreased in A53T SC compared to WT group and tended to increase in A53T EE compared to A53T SC. By alteration of dopamine transporter (DAT) and dopamine receptor 1 (DRD1), EE exposure may normalize dopamine level in striatal dopaminergic nerve terminals and decrease phosphorylated α-Synuclein (aSyn). Also, EE exposure improves the expression of SNARE complex forming genes such as SNAP-25, Syntaxin1 and VAMP-2 downregulated in the striatum of A53T mice. In conclusion, this study suggests that EE induces synaptic plasticity in dopaminergic nerve terminals in striatum and nucleus accumbens and ameliorates non-motor symptoms in pre-motor phase of PD.