Melatonin protects HT-22 cells against palmitic acid-induced glucolipid metabolic dysfunction and cell injuries: Involved in the regulation of synaptic plasticity and circadian rhythms

Abstract

Melatonin (MLT) is ahormonal substance reported with various pharmacological activities.Based on its effects of neuroprotection and metabolic regulation, the aim of the present study is to investigate its potential effect on palmitic acid (PA)-induced cell injuries and glucolipid metabolic dysfunction and explore the possible mechanism. Briefly, HT-22 cells were challenged with PA (0.1 mM, 24 h) and treated with MLT (10−6-10−8 mol/L). Cell proliferation, lipid accumulation and glucose consumption were detected. The protein expression of key molecular involved with the function of synaptic plasticity and circadian rhythms were measured via western blotting, and the expression of Map-2, MT1A, MT1B and Bmal1 were measured via immunofluorescence staining. The results showed that MLT could alleviate the neurotoxicity induced by PA, as indicated by the increased cell proliferation, enhanced fluorescence intensity of Map-2, and decreased lipid deposition and insulin resistance. Moreover, treatment of MLT could reverse the imbalanced expression of p-Akt, p-ERK, Synapsin I, Synaptotagmin I, BDNF, MT1B, Bmal1, and Clock in PA-induced HT-22 cells. These results suggested a remarkably neuroprotective effect of MLT against PA-induced cell injury and glucolipid metabolic dysfunction, the mechanism of which might be involved in the regulation of synaptic plasticity and circadian rhythms.