α-Synuclein reduces surface expressions of NMDA receptors and NMDA-invoked Ca2+ influx and inward current by upregulation of Rab5B in cultured primary hippocampal neurons

doi:10.3969/j.issn.1006-7795.2017.06.018

Journal of Capital Medical University ›› 2017, Vol. 38 ›› Issue (6): 868-873.doi: 10.3969/j.issn.1006-7795.2017.06.018

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α-Synuclein reduces surface expressions of NMDA receptors and NMDA-invoked Ca²⁺ influx and inward current by upregulation of Rab5B in cultured primary hippocampal neurons

Yu Wenjiao^1,2, Yang Weiwei^1,2,3,4, Li Xin^1,2,3,4, Li Xuran^1,2, Chen Min^1,5, Yu Shun^1,2,3,4

1. Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing Institute of Geriatrics, Beijing 100053, China;
2. Clinical Center for Parkinson's Disease, Capital Medical University, Beijing 100053, China;
3. Beijing Key Laboratory for Parkinson's Disease and Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China;
4. National Clinical Research Center for Geriatric Disorders, Beijing 100053;
5. Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China

Received:2017-10-23 Online:2017-11-21 Published:2017-12-16
Supported by:
This study was supported by National Natural Science Foundation of China (81371200, 81071014, 81401042), Beijing Municipal Administration of Hospitals' Mission Plan (SML20150803), Beijing Municipal Science & Technology Commission (Z161100005116011,Z171100000117013), Beijing Municipal Commission of Health and Family Planning (PXM2017_026283_000002), Natural Science Foundation of Guangxi (2014GXNSFAA118197).

Abstract

Abstract: Objective To investigate the effects of α-synuclein(α-Syn) on surface expressions and functions of N-methyl-D-aspartate (NMDA) receptors (NMDARs) in cultured primary hippocampal neurons.Methods Increased intracellular α-Syn levels were realized by extracellular addition of recombinant human α-Syn to the culture medium of rat primary hippocampal neurons. Expressions of surface NMDARs and Rab5B were observed by fluorescence immunocytochemistry and Western blotting. Rab5B antisense oligonucleotides were applied to suppress Rab5B expression. Live cell imaging system and whole-cell patch-clamp recording were used to record NMDA-evoked Ca²⁺ influx and inward currents. Results Neurons treated with α-Syn displayed increased Rab5B, decreased surface NMDARs, and reduced NMDA-evoked Ca²⁺ influx and inward currents. The above α-Syn effects were inhibited by suppression of Rab5B expression.Conclusion α-Syn reduces the surface expression and functions of NMDARs by increasing Rab5B expression.

Key words: α-synuclein, NMDA receptor, Rab5B, neuron, hippocampus

CLC Number:

Q189

Yu Wenjiao, Yang Weiwei, Li Xin, Li Xuran, Chen Min, Yu Shun. α-Synuclein reduces surface expressions of NMDA receptors and NMDA-invoked Ca²⁺ influx and inward current by upregulation of Rab5B in cultured primary hippocampal neurons[J]. Journal of Capital Medical University, 2017, 38(6): 868-873.

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α-Synuclein reduces surface expressions of NMDA receptors and NMDA-invoked Ca²⁺ influx and inward current by upregulation of Rab5B in cultured primary hippocampal neurons

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