Reduced interaction of aggregated α-synuclein and VAMP2 by environmental enrichment alleviates hyperactivity and anxiety in a model of Parkinson’s disease

Kyungri Kim, Soohyun Wi, Jung Hwa Seo, Soonil Pyo, Sung Rae Cho

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson’s disease (PD) is a prevalent motor disease caused by the accumulation of mutated α-synuclein (α-Syn); however, its early stages are also characterized by non-motor symptoms, such as olfactory loss, cognitive decline, depression, and anxiety. The therapeutic effects of environmental enrichment (EE) on motor recovery have been reported, but its effects on non-motor symptoms remain unclear. Herein, we reveal the beneficial effects of EE on PD-related non-motor symptoms and changes in synaptic plasticity in the nucleus accumbens. To investigate its therapeutic effects in the early phase of PD, we randomly assigned eight-month-old mice overexpressing human A53T (hA53T) α-Syn to either the EE or standard condition groups for two months. Next, we performed behavioral tests and biochemical and histological analyses at 10 months of age. EE significantly alleviated locomotor hyperactivity and anxiety during the early stages of PD. It normalized the levels of tyrosine hydroxylase, phosphorylated and oligomeric α-Syn, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex-forming proteins, including synaptosomal-associated protein, 25 kDa, syntaxin1, and vesicle-associated membrane protein 2 (VAMP2). Moreover, the interactions between VAMP2 and pSer129 α-Syn were markedly reduced following EE. The restoration of synaptic vesicle transportation status may underlie the neuroprotective effects of EE in hA53T α-Syn mice.

Original languageEnglish
Article number392
JournalGenes
Volume12
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Bibliographical note

Funding Information:
Funding: This work was supported by grants from the National Research Foundation (NRF-2019R1I1A1A01062098) and the INNOPOLIS Jeonbuk Innovation Cluster, Korea Innovation Foundation (2020-JB-RD-0121), Republic of Korea, and a faculty research grant from Yonsei University College of Medicine (6-2020-0104).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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