Koshy Cherian Ajeesh, Parikh Vinay, Wu Qi, Mao-Draayer Yang, Wang Qin, Blakely Randy D, Sarter Martin
Dept. of Psychology & Neuroscience Program, University of Michigan, Ann Arbor, MI, USA.
Department of Psychology Neuroscience Program, Temple University, Philadelphia, PA, USA.
Neurochem Int. 2017 Sep;108:410-416. doi: 10.1016/j.neuint.2017.05.022. Epub 2017 May 31.
The synaptic uptake of choline via the high-affinity, hemicholinium-3-dependent choline transporter (CHT) strongly influences the capacity of cholinergic neurons to sustain acetylcholine (ACh) synthesis and release. To advance research on the impact of CHT capacity in humans, we established the presence of the neuronal CHT protein in human T lymphocytes. Next, we demonstrated CHT-mediated choline transport in human T cells. To address the validity of T cell-based choline uptake as a proxy for brain CHT capacity, we isolated T cells from the spleen, and synaptosomes from cortex and striatum, of wild type and CHT-overexpressing mice (CHT-OXP). Choline uptake capacity in T cells from CHT-OXP mice was two-fold higher than in wild type mice, mirroring the impact of CHT over-expression on synaptosomal CHT-mediated choline uptake. Monitoring T lymphocyte CHT protein and activity may be useful for estimating human CNS cholinergic capacity and for testing hypotheses concerning the contribution of CHT and, more generally, ACh signaling in cognition, neuroinflammation and disease.
通过高亲和力、依赖半胱氨酸-3的胆碱转运体（CHT）进行的胆碱突触摄取，强烈影响胆碱能神经元维持乙酰胆碱（ACh）合成和释放的能力。为了推进关于CHT能力对人类影响的研究，我们确定了人类T淋巴细胞中存在神经元CHT蛋白。接下来，我们证明了CHT介导的人类T细胞胆碱转运。为了验证基于T细胞的胆碱摄取作为脑CHT能力替代指标的有效性，我们从野生型和CHT过表达小鼠（CHT-OXP）的脾脏中分离出T细胞，并从皮质和纹状体中分离出突触体。CHT-OXP小鼠T细胞中的胆碱摄取能力比野生型小鼠高两倍，这反映了CHT过表达对突触体CHT介导的胆碱摄取的影响。监测T淋巴细胞CHT蛋白和活性可能有助于评估人类中枢神经系统胆碱能能力，并用于检验关于CHT以及更广泛地说ACh信号在认知、神经炎症和疾病中的作用的假设。
