1,25‐Dihydroxyvitamin D₃ administration to 6‐hydroxydopamine‐lesioned rats increases glial cell line‐derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum

Abstract

It has previously been demonstrated that 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] administration, whether in cell cultures or in vivo to rats, increases glial cell line-derived neurotrophic factor (GDNF) expression levels, suggesting that this hormone may have beneficial effects in neurodegenerative disorders. This study was carried out to explore the effects of 1,25(OH)(2)D(3) administration in a 6-OHDA-lesioned rat model of Parkinson's disease on GDNF and tyrosine hydroxylase (TH) expression in substantia nigra (SN) and striatum. Two groups of animals received 1,25(OH)(2)D(3) intraperitoneally, the first group 7 days before the unilateral injection of 6-OHDA into the medial forebrain bundle (MFB) and the second group 21 days (days 21-28) after the unilateral injection of 6-OHDA. Animals of both groups were sacrificed on day 28. In addition, two other groups received a unilateral injection of either saline or 6-OHDA into the MFB. Rats were killed, and the SN and striatum were then removed for GDNF and TH determination. Striatal GDNF protein expression was increased on the ipsilateral with respect to the contralateral side after 6-OHDA injection alone as well as in 1,25(OH)(2)D(3)-treated rats before or after 6-OHDA administration. As expected, 6-OHDA injection induced an ipsilateral decrease in TH-immunopositive neuronal cell bodies and axonal terminals in the SN and striatum. However, treatment with 1,25(OH)(2)D(3) before and after 6-OHDA injection partially restored TH expression in SN. These data suggest that 1,25(OH)(2)D(3) may help to prevent dopaminergic neuron damage.

Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson’s disease, Alzheimer’s disease and autism spectrum disorder

“…In rodents, the neurotoxin 6-hydroxydopamine (6-OHDA) removes dopaminergic neurons in a specific manner and produces PD-like symptoms (Burns et al 1983). There are several studies in rats examining the effects of neuroprotectives to a systemic administration of 6-OHDA (Baluchnejadmojarad et al 2009;Sanchez et al 2009). Similarly, in C. elegans, exposure to 6-OHDA induces programmed cell death in dopaminergic neurons (Cao et al 2005;Nass et al 2002) and complete neuronal destruction if rotenone, a plant neurotoxin in mammals (Alam and Schmidt 2002), was also administered (Schmidt et al 2007).…”

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

“…For detection we used EnVision FLEX/HRP (Dako). Quantitation of immunopositive cells for active caspase-3 expression was performed as previously described (56).…”

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].…”