Mechanism of TRIM32 regulation of synaptic protein expression in the development of epilepsy in a rat model

Accumulating evidence indicates that tripartite motif-containing protein 32 (TRIM32) has important functions in brain physiology and disease. This study investigated the role of TRIM32 in the development of epilepsy and its impact on synaptic remodeling. A rat model of epilepsy was established using pilocarpine with lithium chloride pretreatment and TRIM32 expression was examined by Western blotting and immunohistochemistry. The interaction between TRIM32 and BDNF was assessed by co-immunoprecipitation and immunofluorescence colocalization. TRIM32 knockdown in epileptic rats was achieved by shRNA transfection. Cognitive and anxiety-like behaviors were evaluated using the Y-maze and open-field tests; Western blotting was used to quantify the synaptic proteins PSD-95 and SYN and to assess activity of the BDNF/TrkB/CREB signaling pathway. TRIM32 expression was significantly reduced in epileptic rats. Moreover, TRIM32 knockdown aggravated epilepsy-associated cognitive deficits, impaired open-field performance, and exacerbated synaptic loss. Mechanistically, TRIM32 deficiency intensified these abnormalities through dysregulation of the BDNF/TrkB/CREB pathway. These data suggest that TRIM32 regulates synaptic protein expression in epilepsy and that its deficiency worsens anxiety-like behavior, cognitive impairment, and synaptic loss by perturbing BDNF/TrkB/CREB signaling, thereby providing insights that may inform future therapeutic strategies targeting this signaling pathway.