Ascorbic Acid Neuroprotection Against Hippocampal Injury and Gliosis Induced by E621 in Albino Rats Through Modulation of GFAP, Synaptophysin, and Caspase-3

Monosodium glutamate (E621) is a common flavor enhancer in highly processed food. Although it makes food more enjoyable, chronic intake may lead to excitotoxicity in brain areas. The current study investigates histological and biochemical neurodegenerative alterations in the rat hippocampus following E621 administration and evaluates the potential neuroprotective properties of ascorbic acid (AA) against E621-induced adverse effects. Forty adult male albino rats were divided into four groups: control group (G1), AA group (G2), E621 group (G3), and AA + E621 group (G4). All animals received a daily intraperitoneal (IP) injection for 30 days. Hippocampal samples were processed and stained with hematoxylin and eosin (H&E), immunostained for GFAP, synaptophysin (a synaptic protein), and caspase-3, and biochemically analyzed for oxidative markers, including malondialdehyde (MDA) and superoxide dismutase (SOD). G3 exhibited significant neurodegenerative changes, characterized by pyknotic granular cells and cytoplasmic vacuolation, with significantly elevated GFAP, synaptophysin, and caspase-3 immunoreactivity in the dentate gyrus (DG). These structural deficits correlated with elevated MDA levels and reduced SOD levels in G3. In contrast, simultaneous administration of AA with E621 resulted in substantial preservation of neuronal morphology, a reduction in caspase-3 immunoreactivity, and a restoration of synaptic vesicle density in G4. E621 induces hippocampal injury by increasing ROS levels and dysregulating GFAP, synaptophysin, and caspase-3. At the same time, AA preserves neuronal integrity and synaptic homeostasis, suggesting its potential role as a protective dietary supplement against brain injury induced by the E621 flavor enhancer.