Exploring the Differential Impact of Melatonin Timing Administration (Day vs. Night) on Mitigating Cerebellar Damage Caused by Monosodium Glutamate in Rats.

In tune with the light/dark cycle of the environment, melatonin is secreted on a circadian rhythm. After the lights go out, circulating melatonin levels gradually rise and peak in the middle of the dark phase. Herein, we studied the possible protective timing of melatonin administration on monosodium glutamate-induced cerebellar ataxia in rat models. Thirty-two adult albino male were randomly categorized into four groups: control group, MSG group (4 g/kg/day), day-time melatonin group (MSG + melatonin, 10 mg/kg/day at 9.00 a.m.), and night-time melatonin group (MSG + melatonin, 10 mg/kg/day at 9.00 p.m.). After 10 days of injections, behavioral assessments and serum melatonin were measured. Then rats were sacrificed, cerebellar immunohistopathology, oxidative stress (GPX, GR, NO, iNOS), gene expression of pro-inflammatory genes (PI3K, TNF-α, IL-6) and antioxidant genes (NRF2/HO-1) were assessed. Administration of MSG significantly caused motor deficits, increased levels of NO, INOS, PI3K, TNF-α, and IL-6 levels (p < 0.05), while significantly decreased GPX, GR, NRF2/HO-1, and serum melatonin level (p < 0.05). Histological analysis revealed that MSG exerted degenerative effects, including the presence of pyknotic Purkinje cells, with strong positive reactions for COX2. However, melatonin administration improved these parameters in both treated groups with the superiority of the night melatonin in improving motor behaviors, histological parameters, decreasing COX2 levels, INOS, PI3K, and increasing the expression of NRF2 levels, and increasing the serum melatonin levels. Night-time melatonin administration was more effective in protection against motor incoordination and cerebellar damage than day-melatonin administration.