Vitamin D3 deficiency in puberty rats causes presynaptic malfunctioning through alterations in exocytotic release and uptake of glutamate/GABA and expression of EAAC-1/GAT-3 transporters

Abstract

Recent experimental and epidemiologic investigations have revealed that the central nervous system is a target for vitamin D3 action and also linked vitamin D3 deficiency to Alzheimer's and Parkinson's disease, autism and dementia. Abnormal homeostasis of glutamate and GABA and signaling disbalance are implicated in the pathogenesis of major neurological diseases. Here, key transport characteristics of glutamate and GABA were analysed in presynaptic nerve terminals (synaptosomes) isolated from the cortex of vitamin D3 deficient (VDD) rats. Puberty rats were kept at the VDD diet up to adulthood. VDD caused: (i) a decrease in the initial rates of L-[14C]glutamate and [3H]GABA uptake by plasma membrane transporters of nerve terminals; (ii) a decrease in exocytotic release of L-[14C]glutamate and [3H]GABA; (iii) changes in expression of glutamate (EAAC-1) and GABA (GAT-3) transporters. Whereas, the synaptosomal ambient levels and Ca2+-independent transporter-mediated release of L-[14C]glutamate and [3H]GABA were not significantly altered in VDD. Vitamin D3 is a potent neurosteroid and its nutritional deficiency can provoke development of neurological consequences changing glutamate/GABA transporter expressions and excitation/inhibition balance. Also, changes in glutamate transport can underlie lower resistance to hypoxia/ischemia, larger infarct volumes and worsened outcomes in ischemic stroke patients with VDD.