Mechanistic insights into Quetiapine’s Protective effects on cognitive function and synaptic plasticity in epileptic rats

•Quetiapine improved cognitive function in epileptic rats.•Quetiapine suppressed the expression of MMP-9 in the hippocampus.•Quetiapine activated the CREB/BDNF pathway in the hippocampus.•Quetiapine enhanced synaptic plasticity of neurons in epileptic rats. The study aimed to examine the effects of Quetiapine, an atypical antipsychotic medication with purported neuroprotective qualities, on cognitive function and synaptic plasticity in epileptic rats. This investigation also sought to elucidate the mechanisms by which quetiapine influences the activity of the cyclic adenylate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and metallomatrix proteinase-9 (MMP9) expression in the context of epilepsy. The epileptic model was induced in rats through the administration of pilocarpine, with normal rats serving as the control group. Within the epilepsy group, two subgroups were established: one receiving normal saline and the other receiving quetiapine. Behavioral assays were utilized to assess learning, memory, and spatial exploration abilities. Furthermore, Western blot analysis, immunohistochemistry (IHC), and immunofluorescence (IF) staining were employed to evaluate the activity of the CREB/BDNF pathway, expression of MMP9 protein, and levels of synaptic plasticity-related proteins. Our study revealed that Quetiapine administration led to a notable enhancement in learning and memory in epileptic rats, as indicated by heightened drinking durations and visitation rates in behavioral assessments. Furthermore, Quetiapine upregulated the expression of pro-BDNF, m-BDNF, p-CREB, and CREB within the hippocampus, along with elevating mRNA levels of BDNF and CREB. Additionally, Quetiapine suppressed MMP-9 expression and promoted synaptic plasticity by augmenting SYN and PSD-95 expression levels in the hippocampus. Therefore, Quetiapine improved cognitive functions such as learning, memory, and spatial exploration in epileptic rats. Moreover, Quetiapine activated the CREB/BDNF signaling pathway, suppressed MMP-9 expression, and promoted synaptic plasticity.