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

Cherian, Ajeesh Koshy; Parikh, Vinay; Wu, Qi; Mao-Draayer, Yang; Wang, Qin; Blakely, Randy D.; Sarter, Martin

doi:10.1016/j.neuint.2017.05.022

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…The co-localization of cholinergic lymphocytes and activated macrophages indicated a potential role for targeted ACh delivery to activated macrophages during the later stages of influenza infection. To examine the requirement for ACh during recovery from influenza infection, we disrupt ACh synthesis by treatment with Hemicholinium-3 (HC3) to block the high-affinity choline transporter, the rate-limiting step in ACh synthesis, [61][62][63][64][65][66] during the time period associated with increased ACh concentration ( Figure 1). Mice were infected with influenza A/PR8 (H1N1) as above.…”

Section: Blocking Ach Synthesis Increases Morbiditymentioning

confidence: 99%

<p>Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery</p>

Horkowitz

Schwartz

Álvarez

et al. 2020

ITT

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Introduction This study was designed to explore the role of acetylcholine (ACh) in pulmonary viral infection and recovery. Inflammatory control is critical to recovery from respiratory viral infection. ACh secreted from non-neuronal sources, including lymphocytes, plays an important, albeit underappreciated, role in regulating immune-mediated inflammation. Methods ACh and lymphocyte cholinergic status in the lungs were measured over the course of influenza infection and recovery. The role of ACh was examined by inhibiting ACh synthesis in vivo. Pulmonary inflammation was monitored by Iba1 immunofluorescence, using a novel automated algorithm. Tissue repair was monitored histologically. Results Pulmonary ACh remained constant through the early stage of infection and increased during the peak of the acquired immune response. As the concentration of ACh increased, cholinergic lymphocytes appeared in the BAL and lungs. Cholinergic capacity was found primarily in CD4 T cells, but also in B cells and CD8 T cells. The cholinergic CD4 + T cells bound to influenza-specific tetramers and were retained in the resident memory regions of the lung up to 2 months after infection. Histologically, cholinergic lymphocytes were found in direct physical contact with activated macrophages throughout the lung. Inflammation was monitored by ionized calcium-binding adapter molecule 1 (Iba1) immunofluorescence, using a novel automated algorithm. When ACh production was inhibited, mice exhibited increased tissue inflammation and delayed recovery. Histologic examination revealed abnormal tissue repair when ACh was limited. Conclusion These findings point to a previously unrecognized role for ACh in the transition from active immunity to recovery and pulmonary repair following respiratory viral infection.

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Section: Blocking Ach Synthesis Increases Morbiditymentioning

confidence: 99%

<p>Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery</p>

Horkowitz

Schwartz

Álvarez

et al. 2020

ITT

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“…For the uptake of choline, various transport systems are involved depending on the affinity of choline. A high affinity, hemicholinium-3, and sodium dependent choline transporter (CHT1) has the rate limiting role for the synthesis of ACh [ 95 ]. Mutations in this transporter result in neurological diseases including depression and AD [ 96 ].…”

Section: Slc5a7/cht In the Bbb And Slc44a1/ctl1 In Motor Neuron Diseasementioning

confidence: 99%

Blood–Brain Barrier Solute Carrier Transporters and Motor Neuron Disease

Latif

Kang

2022

Pharmaceutics

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Defective solute carrier (SLC) transporters are responsible for neurotransmitter dysregulation, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We provided the role and kinetic parameters of transporters such as ASCTs, Taut, LAT1, CAT1, MCTs, OCTNs, CHT, and CTL1, which are mainly responsible for the transport of essential nutrients, acidic, and basic drugs in blood–brain barrier (BBB) and motor neuron disease. The affinity for LAT1 was higher in the BBB than in the ALS model cell line, whereas the capacity was higher in the NSC-34 cell lines than in the BBB. Affinity for MCTs was lower in the BBB than in the NSC-34 cell lines. CHT in BBB showed two affinity sites, whereas no expression was observed in ALS cell lines. CTL1 was the main transporter for choline in ALS cell lines. The half maximal inhibitory concentration (IC50) analysis of [3H]choline uptake indicated that choline is sensitive in TR-BBB cells, whereas amiloride is most sensitive in ALS cell lines. Knowledge of the transport systems in the BBB and motor neurons will help to deliver drugs to the brain and develop the therapeutic strategy for treating CNS and neurological diseases.

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Current understanding of cardiovascular autonomic dysfunction in multiple sclerosis

Zahoor,

Pan,

Cerghet

et al. 2024

Heliyon

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

Cited by 4 publications

References 42 publications

<p>Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery</p>

<p>Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery</p>

Blood–Brain Barrier Solute Carrier Transporters and Motor Neuron Disease

Current understanding of cardiovascular autonomic dysfunction in multiple sclerosis

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