Vitamin D is involved in regulating the limbic epileptogenesis

Abstract Limbic epilepsy is a common brain disorder associated with dysregulation of micronutrients, of which vitamin D plays an important role in neuronal survival, neurotransmitter homeostasis, and synaptic transmission. However, the in vivo contribution of vitamin D to epileptogenesis remains unclear. In this study, we observed a significant increase in vitamin D receptor (VDR) mRNA level at 6–12 h after seizure onset in four distinct classic epilepsy models. Vitamin D receptor protein expression also increased following pilocarpine-induced seizures, particularly in the hippocampal granule cell layer. Subsequently, we found that aberrant vitamin D dietary levels could accelerate kindling development. To our surprise, excessive vitamin D intake reduced the frequency of spontaneous seizures in the pilocarpine model, whereas vitamin D deficiency decreased mossy fiber sprouting—a hallmark of epileptogenesis. These findings provide new insights into the mechanisms underlying limbic epileptogenesis.