Optimizing Melatonin Dosage for Neuroprotection in HT22 Hippocampal Neuronal Cells

Abstract

Melatonin is widely studied for its neuroprotective properties in various cellular models, but the optimal dosage for therapeutic effects remains poorly defined, especially in neuronal cell lines like HT22. Discrepancies in the literature regarding effective melatonin concentrations necessitate a systematic investigation to establish a standardized therapeutic window that balances efficacy and safety. The aim is to identify the optimal dosage of melatonin that promotes cell viability and neuroprotection in the HT22 hippocampal neuronal cell line over various exposure times. A quantitative analysis using the MTT assay measured cell viability in HT22 cells treated with increasing concentrations of melatonin (0.1 mM to 5 mM) over time intervals of 24, 48, and 72 h. This approach allowed for the assessment of both the neuroprotective and cytotoxic effects of melatonin across a range of dosages. The study revealed a dose-dependent impact on cell viability, with higher concentrations leading to significant cytotoxic effects. Cell viability was relatively high at lower concentrations (0.1 mM to 0.5 mM) across all time points but showed a marked decline at concentrations exceeding 0.75 mM. The optimal balance between neuroprotection and minimal cytotoxicity was found at doses from 0.1 mM to 0.25 mM. The half-maximal inhibitory concentration (IC 50 ) values indicated increased sensitivity to melatonin over time, decreasing from 0.83 mM at 24 h to 0.39 mM at 72 h. This study successfully defines a more precise therapeutic range for melatonin in HT22 cells, suggesting that lower concentrations (0.1 mM to 0.25 mM) optimize cell viability and neuroprotection without inducing significant cytotoxic effects. These findings contribute to the ongoing effort to standardize melatonin dosages in neurobiological research and clinical applications, potentially influencing.