Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease
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 enrich...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/12/3/392 |
| _version_ | 1797541951964184576 |
|---|---|
| author | Kyungri Kim Soohyun Wi Jung Hwa Seo Soonil Pyo Sung-Rae Cho |
| author_facet | Kyungri Kim Soohyun Wi Jung Hwa Seo Soonil Pyo Sung-Rae Cho |
| author_sort | Kyungri Kim |
| collection | DOAJ |
| description | 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 <i>N</i>-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. |
| first_indexed | 2024-03-10T13:23:50Z |
| format | Article |
| id | doaj.art-0ed1584d18174149a6ed2590ef8be940 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T13:23:50Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0ed1584d18174149a6ed2590ef8be9402023-11-21T09:49:26ZengMDPI AGGenes2073-44252021-03-0112339210.3390/genes12030392Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s DiseaseKyungri Kim0Soohyun Wi1Jung Hwa Seo2Soonil Pyo3Sung-Rae Cho4Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaParkinson’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 <i>N</i>-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.https://www.mdpi.com/2073-4425/12/3/392Parkinson’s diseaseenvironmental enrichmentalpha-synucleinvesicle-associated membrane protein 2nucleus accumbens |
| spellingShingle | Kyungri Kim Soohyun Wi Jung Hwa Seo Soonil Pyo Sung-Rae Cho Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease Genes Parkinson’s disease environmental enrichment alpha-synuclein vesicle-associated membrane protein 2 nucleus accumbens |
| title | Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease |
| title_full | Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease |
| title_fullStr | Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease |
| title_full_unstemmed | Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease |
| title_short | Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease |
| title_sort | reduced interaction of aggregated α synuclein and vamp2 by environmental enrichment alleviates hyperactivity and anxiety in a model of parkinson s disease |
| topic | Parkinson’s disease environmental enrichment alpha-synuclein vesicle-associated membrane protein 2 nucleus accumbens |
| url | https://www.mdpi.com/2073-4425/12/3/392 |
| work_keys_str_mv | AT kyungrikim reducedinteractionofaggregatedasynucleinandvamp2byenvironmentalenrichmentalleviateshyperactivityandanxietyinamodelofparkinsonsdisease AT soohyunwi reducedinteractionofaggregatedasynucleinandvamp2byenvironmentalenrichmentalleviateshyperactivityandanxietyinamodelofparkinsonsdisease AT junghwaseo reducedinteractionofaggregatedasynucleinandvamp2byenvironmentalenrichmentalleviateshyperactivityandanxietyinamodelofparkinsonsdisease AT soonilpyo reducedinteractionofaggregatedasynucleinandvamp2byenvironmentalenrichmentalleviateshyperactivityandanxietyinamodelofparkinsonsdisease AT sungraecho reducedinteractionofaggregatedasynucleinandvamp2byenvironmentalenrichmentalleviateshyperactivityandanxietyinamodelofparkinsonsdisease |