Chlorogenic Acid as a Neuroprotective Agent: Enhancing Plasticity and Promoting Brain Health and Functional Reserve

Introduction: Functional reserve, the process that warrants the brain to have resources to maintain key functions and processes when facing neurodegeneration, may be strengthened in nominally healthy subjects by measures that prompt neural plasticity throughout life. Method: In this work, we administered Chlorogenic Acid (CGA) to evaluate its ability to promote functional morphological plasticity in the frontal cortical-striatal circuit of healthy mice, a pathway exposed constantly to oxidative challenges, excitotoxicity, and neuroinflammation. The magnitude of neural plasticity was estimated by assessing spontaneous motor behavior (open field), the relative magnitude of neuronal activation (number of c-Fos positive neurons), dendritic remodeling (Golgi- Cox impregnation), the availability of Brain-Derived Neurotrophic Factor (BDNF) (semiquantitative Western blotting), and lipid peroxidation (TBARS assay) in CGA- or vehicle-administered C57BL/6 male mice. Results: CGA administration increased c-Fos in the Dorsal striatum (Ds), changed the availability of BDNF and Pro-BDNF in the Frontal Cortex (FC) and DS, induced dendritic remodeling in FC and DS neurons, and reduced FC and DS lipid peroxidation without affecting motor performance or the availability of TrkB receptor isoforms. Conclusion: Our findings suggest that CGA increases functional reserve by promoting neuronal plasticity in healthy male mice. Future research should determine whether these additional resources indeed protect against neurodegeneration.