Overexpression effects of 4.1B protein on epilepsy and excitatory synaptic transmission in mice

Protein 4.1B, part of the evolutionarily conserved protein 4.1 family known for its role as cytoskeletal adaptors, is involved in the localization of NMDA receptors. However, its significance in epilepsy is not well understood. Considering the crucial role of the imbalance between synaptic excitation and inhibition in the development of epilepsy, we proposed that 4.1B might influence the progression of chronic epilepsy by affecting synaptic transmission. Our findings indicated a marked decrease in 4.1B protein levels in the hippocampus and temporal cortex of mice with chronic epilepsy. Immunohistochemical studies showed that 4.1B is mainly found in neurons. Increasing the expression of 4.1B notably lowered the frequency of spontaneous seizures during the chronic phase, and electrophysiological assessments revealed a significant decrease in the amplitude of miniature excitatory postsynaptic currents (mEPSCs). Overall, these results imply that 4.1B plays a role in the development of chronic epilepsy by altering excitatory synaptic transmission and could serve as a potential therapeutic target for epilepsy.