Tannic Acid Mitigates Monosodium Glutamate-Induced Cortical Damage by Modulating Synaptic and Calcium-Related Gene and Protein Expression

Abstract

Neurotoxicity induced by excessive glutamatergic signaling is associated with synaptic dysfunction, calcium imbalance, and oxidative stress, which are key molecular events implicated in several neurodegenerative conditions. Monosodium glutamate (MSG), a common flavor enhancer, may exert neurotoxic effects, particularly on synaptic integrity, though mechanisms remain unclear. Tannic acid (TA), a natural polyphenol, has been proposed as a neuroprotective compound. This study investigated the impact of MSG on synaptic components beyond classical AD markers and assessed the protective potential of TA. Rats were randomly divided into four groups (n = 6 per group) and treated with MSG (2 g/kg) and/or TA (50 mg/kg) by oral gavage for 21 consecutive days. Gene and protein expression levels of the synaptic markers (GRIN2A, GRIN2B, DLG2, SNAP25, SCN2A, and ATP2B2) in the cerebral cortex were analyzed using qPCR and western blot. MSG treatment significantly downregulated SNAP25, GRIN2B, DLG2, and SCN2A at both mRNA and protein levels, indicating synaptic dysfunction. GRIN2A and ATP2B2 showed reduced mRNA expression, but protein levels were inconsistent. MSG+TA group showed no significant difference compared with the control group, while TA alone produced minimal changes, suggesting that its role is primarily protective under toxic stress. These findings suggest that chronic MSG exposure disrupts synaptic molecular architecture, whereas the restorative effect of TA may be attributed to its ability to modulate MSG-induced molecular alterations. The data emphasize synaptic pathways as alternative neurotoxicity targets and highlight TA's potential in mitigating diet-related excitotoxic synaptic alterations. Further functional and pathway-based studies are needed to confirm the underlying mechanisms.