Background: The hippocampus, a key region for learning
and memory, is highly susceptible to excitotoxicity from
excessive glutamate receptor activation, leading to neuronal
injury or death. Monosodium glutamate (MSG), a common
food additive, has been associated with various neurotoxic
and neurodegenerative effects. Materials and Methods:
Adult rats were used to evaluate the protective effects of
vitamin C and melatonin against MSG-induced hippocampal
damage. Sixty rats were divided into five groups: control,
MSG (2 g/kg), VC (MSG + 100 mg/kg vitamin C), ML
(MSG + 10 mg/kg melatonin), and ML+VC (MSG + both
vitamin C and melatonin). Treatments were administered
orally for 28 days. Hippocampal tissues were collected for
histological and immunohistochemical analysis of GFAP,
TNF-α, and caspase-3 expressions. Ethical approval was
obtained from the Institutional Animal Care and Use
Committee (IACUC) of Benha University, Egypt. Results:
MSG exposure significantly increased GFAP, TNF-α, and
caspase-3 expression, indicating neuroinflammation,
apoptosis, and marked histological alterations in the CA1
region. In the VC group, some pyramidal neurons were
distorted with scattered glial cells and vacuolations, whereas
in the ML group, pyramidal neurons were more densely
packed with minimal glial pyknosis and vacuolations.
Combined melatonin and vitamin C treatment largely
preserved hippocampal architecture and markedly reduced
inflammatory and apoptotic markers. Conclusion: MSG exerts pronounced neurotoxic
effects in the rat hippocampus. Co-administration of vitamin C and melatonin produced a
synergistic neuroprotective effect, highlighting their potential to mitigate MSG-induced
hippocampal damage.
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