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Neurochem Int. 2017 Sep;108:410-416. doi: 10.1016/j.neuint.2017.05.022. Epub 2017 May 31.

Hemicholinium-3 sensitive choline transport in human T lymphocytes: Evidence for use as a proxy for brain choline transporter (CHT) capacity.

Author information

1
Dept. of Psychology & Neuroscience Program, University of Michigan, Ann Arbor, MI, USA.
2
Department of Psychology Neuroscience Program, Temple University, Philadelphia, PA, USA.
3
Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
4
Brain Institute and Department of Biomedical Sciences and Brain Institute, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL, USA.
5
Dept. of Psychology & Neuroscience Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: msarter@umich.edu.

Abstract

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.

KEYWORDS:

Acetylcholine; Choline transporter; Genetic CHT variants; Synaptosomes; T lymphocytes

PMID:
28577989
PMCID:
PMC5524217
DOI:
10.1016/j.neuint.2017.05.022
[Indexed for MEDLINE]
Free PMC Article

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