ArticleAlcoholism, clinical and experimental research2020
Molecular Correlates of Topiramate and GRIK1 rs2832407 Genotype in Pluripotent Stem Cell-Derived Neural Cultures.
Article in Alcoholism, clinical and experimental research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 7 citations in OpenAlex.
- GRIK1 genotype and effect of topiramate for alcohol use: a systematic review.Journal of pharmaceutical health care and sciences · 2025Article
- Peripheral myelin protein 2 is underexpressed in early-onset colorectal cancer and inhibits metastasis.Frontiers in molecular biosciences · 2025Article
- Mechanisms of neurodevelopmental toxicity of topiramate.Critical reviews in toxicology · 2024Review
- Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.Brain sciences · 2024Review
- Population pharmacokinetics of topiramate in Chinese children with epilepsy.European journal of clinical pharmacology · 2023Article
- Pharmacogenetics of Addiction Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Induced pluripotent stem cell reprogramming-associated methylation at the GABRA2 promoter and chr4p12 GABAAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
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6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThere is growing evidence that the anticonvulsant topiramate is efficacious in reducing alcohol consumption. Further, an intronic single nucleotide polymorphism (rs2832407, C A) in the GRIK1 gene, which encodes the GluK1 subunit of the excitatory kainate receptor, predicted topiramate's effectiveness in reducing heavy drinking in a clinical trial. The molecular correlates of GRIK1 genotype that may relate to topiramate's ability to reduce drinking remain unknown.
methodsWe differentiated induced pluripotent stem cells (iPSCs) characterized by GRIK1 rs2832407 genotype from 8 A/A and 8 C/C donors into forebrain-lineage neural cultures. Our differentiation protocol yielded mixed neural cultures enriched for glutamatergic neurons. Basal mRNA expression of the GRIK1 locus was examined via quantitative polymerase chain reaction (qPCR). The effects of acute topiramate exposure on excitatory spontaneous synaptic activity were examined via whole-cell patch-clamp electrophysiology. Results were compared and contrasted between iPSC donor genotypes.
resultsAlthough characterization of the GRIK1 locus revealed no effect of rs2832407 genotype on GRIK1 isoform mRNA expression, a significant difference was observed on GRIK1 antisense-2 expression, which was greater in C/C neural cultures. Differential effects of acute exposure to 5 μM topiramate were observed on spontaneous synaptic activity in A/A versus C/C neurons, with a smaller reduction in excitatory event frequency observed in C/C donor neurons.
conclusionsThis work highlights the use of iPSC technologies to study pharmacogenetic treatment effects in psychiatric disorders and furthers our understanding of the molecular effects of topiramate exposure in human neural cells.
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