Calcitriol Protection against Dopamine Loss Induced by Intracerebroventricular Administration of 6-Hydroxydopamine

Abstract

Calcitriol has been implicated as an agent that has neuroprotective effects in various animal models of diseases, possibly by upregulating glial cell line-derived neurotrophic factor (GDNF). The present study examined the neuroprotective effects of calcitriol in a model of early Parkinson's disease. Rats were treated daily with calcitriol or saline for 7 days before an intraventricular injection of 6-hydroxydopamine (6-OHDA), and then for 1 day or daily for 3(1/2) to 4 weeks after lesioning. Evoked overflow and tissue content of dopamine (DA) were determined 3(1/2) to 4 weeks post lesion. The 8-day calcitriol treatment did not attenuate 6-OHDA-induced decreases in evoked overflow of DA, nor did it protect against 6-OHDA-induced reductions in tissue levels of DA in the striatum or substantia nigra. However, the long-term calcitriol treatment did significantly increase evoked overflow of DA, as well as the amount of DA in the striatum, compared to saline treated animals. GDNF was significantly increased in the substantia nigra, but not in the striatum, of non-lesioned, calcitriol treated rats. These results suggest that long-term treatment with calcitriol can provide partial protection for dopaminergic neurons against the effects of intraventricularly administered 6-OHDA.

Association between vitamin D and depressive symptoms varies by season: Results from the German Health Interview and Examination Survey for Adults (DEGS1)

“…Regarding, for example, the effects of vitamin D on nerve growth factor synthesis or neurotransmitter like serotonin, lower levels may contribute to depression (Brown et al, 2003;Cass et al, 2006;Garcion et al, 2002;Smith et al, 2006;Wion et al, 1991). On the other hand, vitamin D deficiency may also be a consequence of depression.…”

“…The presence of vitamin D receptors and vitamin D-activating enzymes in several parts of the human brain known to contribute to the regulation of mood like the hippocampus, hypothalamus and prefrontal cortex provide plausible biological explanations for the relationship between vitamin D deficiency and low mood (Eyles et al, 2005). In addition, there is evidence that vitamin D is a potent inducer of nerve growth factor synthesis (Brown et al, 2003;Wion et al, 1991) and is involved in the expression of monoamines, such as norepinephrine and serotonin, which are associated with depression Garcion et al, 2002;Smith et al, 2006).…”

Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice

“…Vitamin D has been linked to key neurotrophic agents, such as nerve growth factor and glial cell-derived neurotrophic factor [3,4], and animal experiments have suggested that the active form of the vitamin has 'neuroprotective' features. For example, pre-treatment with vitamin D attenuates the effects of various stressors, including 6-hydroxydopamine-induced neurotoxicity [5,6]. Moreover, vitamin D deficiency in adult rats has been shown to exacerbate stroke injuries and lead to more severe post-stroke behavioural impairments and this was accompanied by lower levels of the neuroprotective hormone, insulin-like growth factor 1 [7].…”

“…Links between dopamine and vitamin D have also been identified in adult animals. Vitamin D has been shown to promote the synthesis of tyrosine hydroxylase, the rate-limiting enzyme of dopamine synthesis and also to increase basal levels of dopamine within the central nervous system after localised injection of vitamin D 3 [6,14].…”

Splice Variant Biomarkers for Parkinson's Disease

“…This suggests that dietary regulation of vitamin D may be effective in protecting individuals from PD or slowing PD progression. In animal and cell culture models of PD, vitamin D supplementation was found to be beneficial in slowing disease progression (Wang et al, 2001;Smith et al, 2006;Holick, 2007). In human studies, however, high consumption of food containing vitamin D increased the risk of PD Vitamin C or ascorbate is highly concentrated in the central nervous system and its neuroprotective capabilities show promise in reducing lipid peroxidation levels and increasing catalase activity (Santos et al, 2008).…”