Journal
ACS CHEMICAL NEUROSCIENCE
Volume 13, Issue 17, Pages 2557-2564Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.2c00251
Keywords
alph alpha-synuclein; nicotine; microdialysis; AlphaLISA; Parkinson's disease; A53T
Funding
- NIH [R01 EB003320]
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Understanding the regulation of alpha-synuclein release is crucial for understanding Parkinson's disease. We developed a novel method to monitor alpha-synuclein concentration and found that it is influenced by potassium and nicotine.
Understanding the regulation of alpha-synuclein release could be important in better understanding Parkinson's disease development, progression, and treatment. Advances in such studies are hindered by technical challenges that limit the ability to monitor alpha-synuclein concentration in vivo. We developed a novel alpha-synuclein microdialysis method coupled with a specific and sensitive immunoassay that requires a small sample volume (1 mu L). Using this method, basal alpha-synuclein level was estimated at 254 +/- 78 pM in the striatum of freely moving mice. Additionally, we observed that potassium (75 mM) and nicotine (0.5 mg/kg) administration significantly increased alpha-synuclein in dialysates. These results provide evidence that the methods we report here can be useful to investigate the physiological roles of alpha-synuclein and support the idea that alpha- synuclein is secreted to the extracellular space in a neuronal activity-dependent manner.
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