Neurochemical effects of chronic administration of calcitriol in rats

Abstract

Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

Figure 1

Effect of chronic calcitriol administration on protein expression of vitamin D receptor (VDR) in prefrontal cortex (A); and hippocampus (B). Relative expression values were shown as a normalized ratio to β-actin protein level. Data are means ± SEM (n = 4). * p < 0.05, ** p < 0.01 compared to control group.

Figure 2

Effect of chronic calcitriol administration on mRNA levels of the metabolizing enzymes of the neurotransmitters in prefrontal cortex and hippocampus. Data are means ± SEM (n = 7). * p < 0.05, ** p < 0.01 compared to control group.