Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats

Cass, Wayne A.; Peters, Laura E.; Fletcher, Anita; Yurek, David M.

doi:10.1016/j.neuint.2011.11.010

Cited by 39 publications

(35 citation statements)

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“…Progression of PD symptoms is associated with the degeneration of dopaminergic neurons. As previously outlined, preclinical studies in neurotoxicity animal models of this disease confirm that 1,25(OH) 2 D 3 can restore dopamine levels in striatum and ameliorate dopamine neuron death induced by intra-cerebral administration of 6-OHDA (Wang et al, 2001;Smith et al, 2006;Sanchez et al, 2009;Cass et al, 2012Cass et al, , 2014. Cass et al and Sanchez et al have showed that vitamin D increases GDNF in the lesioned striatum indicating this trophic agent may be the mediating factor for vitamin D's neuroprotective actions on dopamine neurons.…”

Section: 25(oh) 2 D 3 Directly Modulates Th Expression In Neuronal mentioning

confidence: 71%

“…A number of studies have shown that 1,25(OH) 2 D 3 can act as a neuroprotective agent for dopaminergic neurons (Wang et al, 2001;Cass et al, 2006;Smith et al, 2006;Sanchez et al, 2009;Cass et al, 2012Cass et al, , 2014. These data and the epidemiological findings linking low levels of vitamin D with increased risk of Parkinson's disease (PD) (Newmark and Newmark, 2007;Evatt et al, 2008Evatt et al, , 2011Knekt et al, 2010;Peterson et al, 2013) have led to a clinical trials of vitamin D in this disease.…”

Section: 25(oh) 2 D 3 Directly Modulates Th Expression In Neuronal mentioning

confidence: 99%

“…Multiple studies have shown that treatment with the active form of vitamin D, 1,25(OH) 2 D 3 , protects against the adverse effects of the well-known dopaminergic toxin, 6-hydroxydopamine (6-OHDA) (Wang et al, 2001;Smith et al, 2006;Cass et al, 2012Cass et al, , 2014. Cass et al showed that long-term 1,25(OH) 2 D 3 treatment increases the level of glial-derived neurotrophic factor (GDNF) in the damaged striatum.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

et al. 2015

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Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR). The VDR emerges in the rat mesencephalon at embryonic day 12, representing the peak period of dopaminergic cell birth. Our prior studies reveal that developmental vitamin D (DVD)-deficiency alters the ontogeny of dopaminergic neurons in the developing mesencephalon. There is also consistent evidence from others that 1,25(OH)2D3 promotes the survival of dopaminergic neurons in models of dopaminergic toxicity. In both developmental and toxicological studies it has been proposed that 1,25(OH)2D3 may modulate the differentiation and maturation of dopaminergic neurons; however, to date there is lack of direct evidence. The aim of the current study is to investigate this both in vitro using a human SH-SY5Y cell line transfected with rodent VDR and in vivo using a DVD-deficient model. Here we show that in VDR-expressing SH-SY5Y cells, 1,25(OH)2D3 significantly increased production of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. This effect was dose- and time-dependent, but was not due to an increase in TH-positive cell number, nor was it due to the production of trophic survival factors for dopamine neurons such as glial-derived neurotrophic factor (GDNF). In accordance with 1,25(OH)2D3's anti-proliferative actions in the brain, 1,25(OH)2D3 reduced the percentage of dividing cells from approximately 15-10%. Given the recently reported role of N-cadherin in the direct differentiation of dopaminergic neurons, we examined here whether it may be elevated by 1,25(OH)2D3. We confirmed this in vitro and more importantly, we showed DVD-deficiency decreases N-cadherin expression in the embryonic mesencephalon. In summary, in our in vitro model we have shown 1,25(OH)2D3 increases TH expression, decreases proliferation and elevates N-cadherin, a potential factor that mediates these processes. Accordingly all of these findings are reversed in the developing brain in our DVD-deficiency model. Remarkably our findings in the DVD-deficiency model phenocopy those found in a recent model where N-cadherin was regionally ablated from the mesencephalon. This study has, for the first time, shown that vitamin D directly modulates TH expression and strongly suggests N-cadherin may be a plausible mediator of this process both in vitro and in vivo. Our findings may help to explain epidemiological data linking DVD deficiency with schizophrenia.

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Section: 25(oh) 2 D 3 Directly Modulates Th Expression In Neuronal mentioning

confidence: 71%

Section: 25(oh) 2 D 3 Directly Modulates Th Expression In Neuronal mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

et al. 2015

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“…Calcitriol has been shown to increase expression or release of GDNF in various cell lines [14–16] and in vivo administration has been shown to increase expression and protein levels of GDNF in the brain [17–20]. GDNF has potent effects on brain DA systems, and because of this it has been examined in several animal models of PD where it was shown to have neuroprotective or restorative effects [21–25].…”

Section: Introductionmentioning

confidence: 99%

Calcitriol Promotes Augmented Dopamine Release in the Lesioned Striatum of 6-Hydroxydopamine Treated Rats

et al. 2014

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Current therapies for Parkinson's disease (PD) offer symptomatic relief but do not provide a cure or slow the disease process. Treatments that could halt progression of the disease or help restore function to damaged neurons would be of substantial benefit. Calcitriol, the active metabolite of vitamin D, has been shown to have significant effects on the brain. These effects include upregulating trophic factor levels, and reducing the severity of some central nervous system lesions. While previous studies have shown that calcitriol can be neuroprotective in 6-hydroxydopamine (6-OHDA) rodent models of PD, the present experiments were designed to examine the ability of calcitriol to promote restoration of extracellular DA levels and tissue content of DA in animals previously lesioned with 6-OHDA. Male Fischer-344 rats were given a single injection of 12 µg 6-OHDA into the right striatum. Four weeks later the animals were administered vehicle or calcitriol (0.3 or 1.0 µg/kg, s.c.) once a day for eight consecutive days. Three weeks after the calcitriol treatments in vivo microdialysis experiments were conducted to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in both potassium and amphetamine evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. In animals treated with 6-OHDA followed by calcitriol there was significantly greater potassium and amphetamine evoked overflow of DA from the lesioned striatum compared to that from the control animals. The calcitriol treatments also led to increases in postmortem tissue levels of DA in the striatum and substantia nigra. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons.

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“…In rats, vitamin D has been shown to protect against methamphetamine-induced reductions in dopamine and serotonin in both the striatum and accumbens (Cass et al, 2006). Vitamin D treatment has also been shown to increase both potassium-and amphetamine-evoked overflow of striatal dopamine as well as increase substantia nigra tissue levels of dopamine and its main metabolites (Cass et al, 2012).…”

Section: Neurotransmissionmentioning

confidence: 99%

The role of adult vitamin D deficiency in cognition and brain function in mice

Groves¹

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Vitamin D deficiency is prevalent throughout the world. Even in a temperate climate such as Australia, one-third of the adult population has insufficient levels of serum vitamin D (25-hydroxyvitamin D levels <50 nmol/L). Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality; they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The use of animal experiments can examine the biological plausibility of the relationship between vitamin D deficiency and adverse brain outcomes.Vitamin D is a neurosteroid that has a wide range of functions within the brain including calcium maintenance, regulation of neurotrophic factors, neurogenesis, and neuroprotection. Using a model of adult vitamin D (AVD) deficiency in BALB/c mice, we have previously shown alterations in a range of behaviours and an imbalance between excitatory and inhibitory neurotransmission, which may be relevant to a range of neuropsychiatric disorders. Therefore, we have provided experimental evidence demonstrating that vitamin D deficiency in adulthood impacts on a range of brain functions, and is therefore a biologically plausible risk factor for the development of neuropsychiatric disorders. However, there is currently insufficient evidence to account for the mechanism(s) by which this occurs.There were four main aims of the thesis; to determine whether AVD deficiency impacts on (1) cognition, (2) adult hippocampal neurogenesis, and (3) glutamate and GABA signaling in BALB/c mice; and to determine if AVD deficiency would (4) exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6J mice.To address these aims I assessed attentional processing in BALB/c mice using the 5 choice serial reaction time task and found sex-dependent impairments in AVD-deficient male mice only.Structural and diffusion tensor imaging was assessed using MRI in male mice, however we found no significant alterations in gross brain structure or connectivity within the brain in the group exposed to AVD deficiency. I used immunohistological techniques to assess two measures of hippocampal neurogenesis, cell proliferation and survival of newborn neurons, and found that hippocampal neurogenesis was not affected by AVD deficiency at baseline or following wheel running stimulated neurogenesis.iii Despite no cellular level change in neurogenesis, the analysis of the proteomics of the hippocampus, although preliminary, provided clues that AVD deficiency may have an effect on synapse formation and plasticity, and dendritic arborisation and that these changes may be responsible for impaired learning and memory. The proteomics also provided convergent evidence of an effect on glutamate and...

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Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats

Cited by 39 publications

References 44 publications

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

Calcitriol Promotes Augmented Dopamine Release in the Lesioned Striatum of 6-Hydroxydopamine Treated Rats

The role of adult vitamin D deficiency in cognition and brain function in mice

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