Syringic Acid Converts Poor Learning Mice to Good Learners: Insinuations for Memory Enhancement

This study investigates the role of syringic acid (SA) in enhancing cognitive function by improving poor-learning mice, which exhibit reduced expression of plasticity-related molecules and diminished activation of cAMP Response Element-Binding Protein (CREB), a key transcription factor involved in memory consolidation. The aim was to explore whether SA could improve learning ability by modulating neuronal signaling pathways linked to synaptic plasticity. N2a neuronal cells were treated with SA to evaluate the expression of plasticity-related molecules and to assess the involvement of Protein Kinase A (PKA) and calcium influx in neuronal signaling. For in vivo analysis, mice were classified as good and poor learners based on their performance in the Barnes maze test. Poor-learning mice were further divided into three groups: control, SA-treated, and vehicle-treated, while good learners served as an additional control group. Behavioral tests were performed to assess cognitive performance, and brain tissues were analyzed for the expression of plasticity markers, NMDA/AMPA-mediated calcium influx, and activation of CREB and Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α). SA significantly enhanced calcium influx through NMDA and AMPA receptors and upregulated plasticity-related molecules via PKA activation. Additionally, SA-induced activation of PPARα further promoted PKA, resulting in increased CREB phosphorylation. In poor-learning mice, SA administration restored CREB activity and plasticity-related molecules during memory consolidation, leading to improved learning performance. SA enhances neuronal plasticity and cognitive function by targeting the PPARα-PKA-CREB signaling axis, indicating its potential as a novel therapeutic potential of SA for cognitive enhancement.