ArticleMolecular neurobiology2025
E4BP4-Driven Circadian SLC6A1 Expression Governs Tiagabine Chronoefficacy in Temporal Lobe Epilepsy.
Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Physical exercise and inflammation in Parkinson's disease: a review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temporal lobe epilepsy (TLE), the most prevalent form of focal epilepsy and a leading cause of surgically managed intractable cases, is characterized by rhythmic spontaneous seizures that exhibit underutilized therapeutic potential. Here, we aim to uncover the impact of dosing time on the anticonvulsant effect of tiagabine and to elucidate the underlying mechanisms involved. Tiagabine markedly attenuated seizure severity and progression in both acute and chronic models of pilocarpine-induced TLE. Pharmacological effects of tiagabine were found to vary according to dosing time, demonstrating greater efficacy during the light phase compared to the dark phase. This variation in tiagabine efficacy was attributed to diurnal fluctuations in GABAergic neurotransmission, which depends on SLC6A1-dependent GABA reuptake rhythm. Notably, ablation of circadian transcription factor E4bp4 abolished SLC6A1 expression rhythms and abrogated the chronoefficacy of tiagabine. Further, our findings indicated that E4BP4-driven circadian oscillations in SLC6A1 expression regulated the efficacy of tiagabine in a circadian time-dependent manner. These results advocated for chronotherapeutic optimization of tiagabine dosing schedules to align with endogenous SLC6A1 rhythms, offering a promising avenue for precision medicine in the management of TLE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.