Role of melatonin receptors in the effects of melatonin on BDNF and neuroprotection in mouse cerebellar neurons

Although melatonin affects developing neurons and is neuroprotective, a role of melatonin receptors termed MT1 and MT2 in these actions is unclear. We investigated the effects of melatonin on the levels of the brain derived neurotrophic factor (BDNF) in the developing cerebellum and cerebellar granule cells (CGC) of wild-type (WT), MT1- and MT2-knockout mice. A model of low-potassium CGC toxicity was used to evaluate neuroprotection. A 14-day-old pups and CGC cultures were treated with melatonin; 0.01 mg/kg intraperitoneally and 1 nM in vitro, respectively. Treatment of WT pups and CGC with melatonin did not alter BDNF levels. The absence of MT2 but not MT1 receptors enabled melatonin to increase cerebellar and CGC BDNF content. Nanomolar melatonin was neuroprotective in MT2-knockout but not WT CGC. We propose that CGC from MT2-knockout mice could serve as a model for studying the influence of melatonin on human CGC, which express MT1 but not MT2 receptors.