MODULATION OF CORTICOSTRIATAL SYNAPTIC RESPONSE BY CAFFEIC ACID: EFFECTS ON LIGAND-GATED CONDUCTANCES OF IONOTROPIC GLUTAMATE AND GABA RECEPTORS

Caffeic acid (CA) is a phenolic compound found in a wide variety of vegetables and plants. It is recognized for its biological activity, exhibiting properties that are antioxidant, antiviral, anti-inflammatory, anticancer, immunomodulatory, and neuroprotective. Research indicates that CA promotes cell survival against toxicity induced by β-amyloid aggregates and neurotoxic agents such as acrolein. Additionally, CA enhances cell differentiation triggered by Nerve Growth Factor (NGF), a process believed to activate intracellular signaling pathways, particularly MEK/ERK.
In our laboratory, we have observed that CA modulates the population synaptic response (PSR) of the corticostriatal pathway and mitigates neurotoxic damage induced by 3-NP. Notably, the PSR consists of both GABAergic and glutamatergic components. Therefore, this study aims to determine whether CA alters ligand-gated conductances in ionotropic glutamate receptors (NMDA and AMPA/kainate) as well as in GABAergic (GABA_A) receptors.
For this investigation, we used 5-week-old C57BL/6 mice. Brain tissue was processed to obtain 300 µm sagittal slices, where we performed electrophysiological recordings using the whole-cell voltage-clamp technique. The results indicate that CA induces a concentration-dependent modulation of the PSR, affecting both glutamatergic and GABAergic synaptic responses.
Furthermore, to investigate the molecular mechanisms underlying these effects, we evaluated if CA stimulates ERK signalling pathway in our experimental conditions. The time-course of ERK 1/2 activation of CA shows that it induces ERK 1/2 phosphorylation, reaching peak activation levels after 3 minutes of incubation. These findings suggest that CA modulates the MEK/ERK signaling pathway to modulate striatal ligand-gated conductances.
This work was supported by Grant IN206324, DGAPA-PAPIIT, UNAM