Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Chem Neurosci. 2022 Sep 7;13(17):2557-2564. doi: 10.1021/acschemneuro.2c00251. Epub 2022 Aug 12.
Understanding the regulation of α-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 α-synuclein concentration in vivo. We developed a novel α-synuclein microdialysis method coupled with a specific and sensitive immunoassay that requires a small sample volume (1 μL). Using this method, basal α-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 α-synuclein in dialysates. These results provide evidence that the methods we report here can be useful to investigate the physiological roles of α-synuclein and support the idea that α-synuclein is secreted to the extracellular space in a neuronal activity-dependent manner.
了解α-突触核蛋白的释放调控对于更好地理解帕金森病的发展、进展和治疗可能非常重要。此类研究的进展受到技术挑战的限制，这些挑战限制了在体内监测α-突触核蛋白浓度的能力。我们开发了一种新的α-突触核蛋白微透析方法，与一种特异性和灵敏性的免疫测定法相结合，该方法需要的样本量很小（1 μL）。使用该方法，在自由活动的小鼠纹状体中，α-突触核蛋白的基础水平估计为 254 ± 78 pM。此外，我们观察到钾（75 mM）和烟碱（0.5 mg/kg）给药显著增加了透析液中的α-突触核蛋白。这些结果提供了证据，证明我们在这里报告的方法可用于研究α-突触核蛋白的生理作用，并支持α-突触核蛋白以神经元活动依赖性方式分泌到细胞外空间的观点。
