Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters
| Autor: | Hyongbum Kim, Jae Yong Choi, Min Young Lee, Tae Hyun Choi, Chul Hoon Kim, Bae Hwan Lee, Chi Hoon Yi, Myung Sun Kim, Young Hoon Ryu, Jung Hwa Seo, Jong Eun Lee, Ji Hea Yu, Sung Rae Cho |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Striatal dopamine media_common.quotation_subject Environment Mice 03 medical and health sciences 0302 clinical medicine mental disorders parasitic diseases Animals Phosphorylation Internalization Protein Kinase C Dopamine transporter media_common Dopamine Plasma Membrane Transport Proteins Environmental enrichment Neuronal Plasticity biology Transporter Original Articles Corpus Striatum Endocytosis 030104 developmental biology nervous system Neurology Biotinylation Synaptic plasticity biology.protein Neurology (clinical) Cardiology and Cardiovascular Medicine Psychology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 36:2122-2133 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1177/0271678x15613525 |
| Popis: | Environmental enrichment (EE) with a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral function. However, the mechanism remains to be elucidated in detail. We aimed to investigate dopamine-related synaptic plasticity underlying functional improvement after EE. For this, six-week-old CD-1 mice were randomly allocated to EE or standard conditions for two months. EE significantly enhanced behavioral functions such as rotarod and ladder walking tests. In a [18F]FPCIT positron emission tomography scan, binding values of striatal DAT were significantly decreased approximately 18% in the EE mice relative to the control mice. DAT inhibitor administrated to establish the relationship of the DAT down-regulation to the treatment effects also improved rotarod performances, suggesting that DAT inhibition recapitulated EE-mediated treatment benefits. Next, EE-induced internalization of DAT was confirmed using a surface biotinylation assay. In situ proximity ligation assay and immunoprecipitation demonstrated that EE significantly increased the phosphorylation of striatal DAT as well as the levels of DAT bound with protein kinase C (PKC). In conclusion, we suggest that EE enables phosphorylation of striatal DAT via a PKC-mediated pathway and causes DAT internalization. This is the first report to suggest an EE-mediated mechanism of synaptic plasticity by internalization of striatal DAT. |
| Databáze: | OpenAIRE |
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