Work

TCF7L2 transcriptionally regulates C1QB to exacerbate synaptic pruning-dependent neuronal injury in the epileptic hippocampus

Year: 2026

Type: article

Abstract: Epilepsy represents one of the most prevalent and debilitating chronic neurological disorders. While the complement component 1q subcomponent B (C1QB) has been implicated in synaptic pruning and is associated with various neurological diseases, including epilepsy, the transcriptional regulatory mechanisms of the C1QB gene in epilepsy remain poorly understood. Here, we identified transcription factor 7-like 2 ( TCF7L2 ) as a novel upstream transcriptional regulator of C1QB gene. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays confirmed the direct binding of TCF7L2 to the C1QB promoter region and its positive regulatory effect on C1QB expression in vitro. Using a kainic acid-induced epilepsy model in male C57BL/6 mice, we demonstrated a significant upregulation of both Tcf7l2 and C1qb in the hippocampal region, which was accompanied by microglial activation and neuronal damage. Notably, the lentivirus-mediated specific knockdown of Tcf7l2 effectively reversed the overexpression of C1qb , attenuated microglial activation, and ameliorated neuronal injury in epileptic mice. Our study establishes the TCF7L2-C1QB regulatory axis and demonstrates its pathogenic role in epilepsy, suggesting that targeting this pathway may offer a novel therapeutic strategy for epilepsy treatment. • Identification of TCF7L2 as a Novel Upstream Regulator of C1QB in Epilepsy • Direct Binding of TCF7L2 to the C1QB Promoter • Reversal of C1QB Upregulation and Synaptic Defects via TCF7L2 Knockdown • First Evidence of the TCF7L2-C1QB Axis in Regulating Synaptic Pruning

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2026.111730

Authors: Lulu Wu, Yuping Huang, Xinyu Wang, Ting Tian, Dandan Feng, Guoping Zhou

Institutions: Jiangsu Province Hospital, Nanjing Medical University, Second Affiliated Hospital of Nanjing Medical University

Language: English

Topic: Epilepsy research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280