ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Choline transporter 1 maintains cholinergic function in choline acetyltransferase haploinsufficiency.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Brain proton magnetic resonance spectroscopy and neurodevelopment after preterm birth: a systematic review.Pediatric research · 2022Pooled it
- Estren prevents beta-amyloid-induced basal forebrain cholinergic loss and long-term spatial memory deficits in aged female mice.Scientific reports · 2026Article
- The Central Cholinergic Synapse: A Primer.International journal of molecular sciences · 2025Review
- Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.Aging and disease · 2025Review
- Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum.Journal of neuroinflammation · 2023Article
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- Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function.International journal of molecular sciences · 2021Review
- Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects theInternational journal of molecular sciences · 2020Article
- Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF.Frontiers in neuroscience · 2019Review
- Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Involvement of Cholinergic Dysfunction and Oxidative Damage in the Effects of Simulated Weightlessness on Learning and Memory in Rats.BioMed research international · 2018Article
- Genistein Ameliorates Scopolamine-Induced Amnesia in Mice Through the Regulation of the Cholinergic Neurotransmission, Antioxidant System and the ERK/CREB/BDNF Signaling.Frontiers in pharmacology · 2018Article
- Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter.Frontiers in molecular neuroscience · 2017Article
- Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice.Metabolic brain disease · 2016Article
- Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson's Disease.Journal of molecular neuroscience : MN · 2016Article
- Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.Neurology · 2016Article
- Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice.BMC complementary and alternative medicine · 2016Article
- RECENT DEVELOPMENTS IN ELECTROCHEMICAL SENSORS FOR THE DETECTION OF NEUROTRANSMITTERS FOR APPLICATIONS IN BIOMEDICINE.Analytical letters · 2015Article
- Cholinergic activity as a new target in diseases of the heart.Molecular medicine (Cambridge, Mass.) · 2015Review
- Modeling the Interaction between β-Amyloid Aggregates and Choline Acetyltransferase Activity and Its Relation with Cholinergic Dysfunction through Two-Enzyme/Two-Compartment Model.Computational and mathematical methods in medicine · 2015Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine (ACh), is thought to be present in kinetic excess in cholinergic neurons. The rate-limiting factor in ACh production is the provision of choline to ChAT. Cholinergic neurons are relatively unique in their expression of the choline transporter 1 (CHT1), which exhibits high-affinity for choline and catalyzes its uptake from the extracellular space to the neuron. Multiple lines of evidence indicate that the activity of CHT1 is a key determinant of choline supply for ACh synthesis. We examined the interaction of ChAT and ChT activity using mice heterozygous for a null mutation in the Chat gene (Chat+/-). In these mice, brain ChAT activity was reduced by 40-50% relative to the wild type, but brain ACh levels as well as ACh content and depolarization-evoked ACh release in hippocampal slices were normal. However, the amount of choline taken up by CHT1 and ACh synthesized de novo from choline transported by CHT1 in hippocampal slices, as well as levels of CHT1 mRNA in the septum and CHT1 protein in several regions of the CNS, were 50-100% higher in Chat+/- than in Chat+/+ mice. Thus, haploinsufficiency of ChAT leads to an increased expression of CHT1. Increased ChT activity may compensate for the reduced ChAT activity in Chat+/- mice, contributing to the maintenance of apparently normal cholinergic function as reflected by normal performance of these mice in several behavioral assays.
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