EFFECTS OF CHLOROGENIC ACID ON SYNAPTIC PLASTICITY AND NEUROPROTECTION IN A 3-NITROPROPIONIC ACID-INDUCED NEURODEGENERATION MODEL

Chlorogenic acid (CGA) is a polyphenolic compound explored for its potential to prevent neuronal loss in neurodegenerative diseases due to its antioxidant, anti-inflammatory, and neuroprotective properties. The exact mechanisms of neuroprotection are not fully understood, but activation of signaling pathways like ERK1/2 and metabolites from gut microbiota may play a role.
This study evaluated the effects of systemic CGA administration (100 mg/kg, i.p.) on striatal synaptic activity and neuronal morphology in a neurodegeneration model induced by 3-nitropropionic acid (3-NP, 15 mg/kg, i.p.). It also analyzed changes in gut microbiota and ERK1/2 phosphorylation to elucidate neuroprotective mechanisms.
Male mice of the C57BL/6 strain, aged 5 weeks, were used. The animals were randomly assigned to four groups: Control, CGA, 3-NP, and CGA+3-NP (n=12 per group) for 5 days of treatment. Following treatment, half underwent morphological analysis while others provided fecal and brain samples for microbiota and electrophysiological studies.
High-frequency stimulation (HFS) in control tissue led to long-term depression (LTD), whereas the 3-NP group showed long-term potentiation (LTP). CGA and CGA+3-NP treatments prevented changes in synaptic response amplitude. CGA also affected ERK1/2 expression and phosphorylation, suggesting that it might activate homeostatic plasticity mechanisms in the striatum, reducing excitotoxicity in the 3-NP model linked with lower synaptic spiny density and altered microbiota diversity.

Acknowledgments: Authors thank The Mass Sequencing Unit of the National Laboratory in Health FES-Iztacala, UNAM, México. This work was sopporte by the Grant No. IN206324, DGAPA-PAPIIT, UNAM to EHE.