1,25-dyhydroxyvitamin D3 Attenuates l-DOPA-Induced Neurotoxicity in Neural Stem Cells

Abstract

The neurotoxicity of levodopa (L-DOPA) on neural stem cells (NSCs) and treatment strategies to protect NSCs from this neurotoxicity remain to be elucidated. Recently, an active form of vitamin D3 has been reported to display neuroprotective properties. Therefore, we investigated the protective effect of 1,25-dyhydroxyvitamin D3 (calcitriol) on L-DOPA-induced NSC injury. We measured cell viability via the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays and Annexin V/PI staining followed by flow cytometry, cell proliferation using the BrdU and colony-forming unit (CFU) assays, cell differentiation via immunocytochemistry, the levels of free radicals via 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, apoptosis via DAPI and TUNEL staining, and intracellular signaling protein expression via Western blot. Antibody microarrays were also employed to detect changes in the expression of prosurvival- and death-related proteins. Treatment of NSCs with L-DOPA reduced their viability and proliferation. This treatment also increased the levels of free radicals and decreased the expression levels of intracellular signaling proteins that are associated with cell survival. However, simultaneous exposure to calcitriol significantly reduced these effects. The calcitriol-mediated protection against L-DOPA toxicity was blocked by the phosphoinositide 3-kinase (PI3K) inhibitor LY294004. L-DOPA also inhibited the expression of Nestin and Ki-67, and co-treatment with calcitriol alleviated these effects. The expression levels of GFAP, DCX, and Tuj1 were not significantly affected by treatment with L-DOPA or calcitriol. Calcitriol protects against L-DOPA-induced NSC injury by promoting prosurvival signaling, including activation of the PI3K pathway, and reducing oxidative stress.

Effects of calcitriol on experimental spinal cord injury in rats

“…It was reported that calcitriol can significantly decrease apoptosis in levodopa-induced neural stem cell injury. 9 In addition, similar therapeutic effects were confirmed in an in vitro model of Parkinson's disease. 10 Therefore, calcitriol treatment reduces Effects of calcitriol on SCI K-l Zhou et al the level of cell apoptosis in many diseases.…”

“…8 Calcitriol attenuates levodopa-induced neurotoxicity in neural stem cells by significantly reducing apoptosis. 9 In addition, calcitriol has been reported to upregulate the level of cellular autophagy. 10 However, its relevance to promotion of functional recovery after SCI in rats has not been reported.…”

Hypovitaminosis D predicts the onset of orthostatic hypotension in older adults

“…7 Moreover, it seems that the active form of vitamin D could activate p38 mitogen-activated protein kinase and phosphatidylinositol kinase 24 , which induces oxidative stress and consequently a structural disintegration and stiffening of the arterial wall. 25 Altogether these findings suggest that low vitamin D levels could play a role in reducing compliance in arteries making difficult the adaptation during standing up. Second, some research have shown that hypovitaminosis D could be associated with a dysfunction of the baroreflex neural arc (i.e.…”

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease

“…Recently, many studies of PD models have demonstrated roles for vitamin D in neuronal cell differentiation and neuroprotection via various mechanisms [17,18,19,20,21]. Therefore, vitamin D may be neuroprotective against PD-related degenerative processes in the dorsal motor vagal system and enteric nervous system, indicating that vitamin D plays an important role in gastric dysmotility in PD.…”

“…However, several studies have demonstrated an additional role for vitamin D in neuroprotection through various mechanisms, including antioxidation, neuronal calcium regulation, immunomodulation, enhanced nerve conduction, detoxification and autophagy [16,17,18,19,20,21]. Furthermore, vitamin D has recently been suggested to be involved in the pathogenesis and progression of PD [22], and recently, we reported that vitamin D levels were associated with orthostatic hypotension in PD patients [23].…”