ASSESSMENT OF THE HISTOARCHITECTURAL CHANGES IN THE HYPOTHALAMUS OF ADULT FEMALE WISTAR RATS FOLLOWING CHRONIC LOW-DOSE ORAL MONOSODIUM GLUTAMATE EXPOSURE

Monosodium glutamate (MSG) is a commonly used flavor enhancer in the global food industry, yet its safety remains controversial due to emerging evidence of neurotoxicity, particularly in vulnerable brain regions such as the hypothalamus. This study investigates the histoarchitectural alterations induced in the hypothalamus of adult female Wistar rats following chronic low-dose oral exposure to MSG, emphasizing potential sex-specific neurotoxic effects. The hypothalamus plays a central role in regulating endocrine, metabolic, and reproductive functions and is especially sensitive to excitotoxic and oxidative insults due to its incomplete blood-brain barrier. Fifteen adult female Wistar rats were randomly assigned into three groups (n=5 per group): a control group receiving 1 ml of distilled water, a low-dose MSG group (30 mg/kg), and a high-dose MSG group (100 mg/kg). Treatments were administered orally via gavage once daily for 60 consecutive days. At the end of the experiment, body and brain weights were measured, and the hypothalamic tissues were harvested, processed, and analyzed histologically using hematoxylin and eosin staining. Sections were examined under light microscopy at multiple magnifications (×40, ×100, ×400), and findings were compared across groups. Results indicated a dose-dependent increase in body weight, particularly in the high-dose MSG group, suggesting disrupted hypothalamic regulation of appetite and energy homeostasis. Although brain weight showed no statistically significant differences across groups (p>0.05), histological analysis revealed progressive and marked neurodegeneration in MSG-treated animals. In the 30 mg/kg group, mild neuronal shrinkage, early pyknosis, reduced neuronal density, and moderate glial cell proliferation were observed, indicating early excitotoxic and inflammatory responses. In contrast, the 100 mg/kg group displayed severe neuronal loss, cytoplasmic vacuolation, densely packed reactive glial cells (gliosis), disrupted neuropil architecture, and enlarged perivascular spaces—hallmarks of chronic neuroinflammation, oxidative damage, and edema. These histoarchitectural changes correlated with prior literature linking MSG exposure to glutamate receptor overstimulation, mitochondrial dysfunction, and compromised neuronal integrity. This study demonstrates that even low-dose chronic MSG intake can result in significant hypothalamic neurotoxicity in adult female rats. The observed damage likely impairs neuroendocrine signaling pathways governing metabolism, stress response, and reproductive function. Notably, the use of a female model highlights potential hormonal modulation of MSG toxicity, with implications for women's health—particularly regarding fertility and metabolic disorders. These findings emphasize the need for sex-specific risk assessments of food additives and call for tighter regulatory scrutiny of chronic dietary MSG consumption. Future studies should investigate molecular pathways of damage and evaluate antioxidant or neuroprotective interventions aimed at mitigating MSG-induced hypothalamic injury.