Michael et al., Cell Dev Biol 2013, 2:4
DOI: 10.4172/2168-9296.1000127
Volume 2 • Issue 4 • 1000127
Cell Dev Biol
ISSN: 2168-9296 CDB, an open access journal
Open Access Research Article
VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic
Process Formation in Melanocyte Model for Pigmented Cells in
Parkinsonism
Ogundele Olalekan Michael
1
*, Ajonijebu
2
, Duyilemi Chris
3
, Okunnuga Adedotun Adetokunbo
4
, Adekeye Adeshina Oloruntoba
1
and Ojo
Abiodun Ayodele
4
1
Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Nigeria
2
Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Nigeria
3
Department of Morbid Anatomy and Histopathology, Federal Medical Centre, Nigeria
4
Department of Chemical Sciences, College of Sciences, Afe Babalola University, Nigeria
Abstract
Background: A major cellular change in dopaminergic neurons leading to Parkinsonism is the alteration
of microtubule proteins that causes accumulation of tau protein, α-syn and β-amyloid plaque in the cells. In this
study we investigate the role of Vitamin D
3
in relieving the symptoms of Parkinsonism as it is capable of stimulating
polymerization of microtubules. The Microtubules (MT) system in the fsh scale melanocytes has been modeled for
the dopaminergic neurons of the Substantia Nigra (SN). These cells are capable of forming cellular processes similar
to what is seen in the dopaminergic neurons; in this study, we investigate the protective effect of Vitamin D
3
Receptor
Agonist (VDRA) and N-Methyl-D-Aspartate Receptor (NMDA R) inhibition in process formation, synaptic denervation
and melanin loss in fsh scale melanocytes modeled as pigmented adrenergic cells.
Method: The Tilapia scale was isolated and sub cultured in Ringer’s solution following which the cells were
prepared for imaging. We incubated the cells with VDRA, Ketamine and a combination of Ketamine and VDRA in
separate set ups for 60 minutes. Using brightfeld imaging techniques, the cells were viewed during the incubation
period and recorded using a Cameroscope connected to a computer interface.
Results/Conclusion: The cells incubated with VDRA and NMDA R inhibitor, showed an increase in the number
of process and extent of the process formation; the increased number of process is an indication of a rapid rate of
polymerization of microtubules. Also, the processes formed are combined long processes peculiar to the NMDA R1
inhibition and short processes characteristic of VDR potentiation as seen in VDRA treatment only. Most of the effects
of the VDRA were restricted to process formation around the cell body; this is similar to the microtubule cytoskeletal
system found in the dendritic nucleation assembly. This fnding confrms the presence of VDR and its likely restriction
to d cell body plus its role in facilitating short dendrite-like process formation while NMDA R is located on the processes
and facilitates long process formation.
*Corresponding author: Ogundele OM, Department of Anatomy, College
of Medicine and Health Sciences, Afe Babalola University, Nigeria, Tel:
+234(0)7031022702; E-mail: ola.ogundele@abuad.edu.ng
Received September 01, 2013; Accepted October 24, 2013; Published October
26, 2013
Citation: Michael OO, Ajonijebu, Chris D, Adetokunbo OA, Oloruntoba AA, et al.
(2013) VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic Process
Formation in Melanocyte Model for Pigmented Cells in Parkinsonism. Cell Dev Biol
2: 127. doi:10.4172/2168-9296.1000127
Copyright: © 2013 Michael OO, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Keywords: Parkinsonism; Melanocytes; Microtubules; Pigment;
Dopamine; Neurons; Vitamin D; Neurodegeneration
Abbreviations: ACSF: Artifcial Cerebrospinal Fluid; VDR: Vitamin
D
3
Receptor; VDRA: Vitamin D
3
Receptor Agonist; ATP: Adenosine
Trios Phosphate; DNA: Deoxyribonucleic Acid; NMDA R: N-Methyl-
D-Aspartate Receptor; PD: Parkinson Disease; SN: Substantia Nigra;
MT: Microtubule; MTOC: Microtubule Organization Centre; NDD:
Neurodegenerative Disease
Introduction
Selective vulnerability of the dopaminergic neurons and pigment
cells of the SN cannot be over emphasized in the etiology and progression
of PD. Defciency of Vitamin D
3
or genetic mutations involving the
VDR have been described in multi array organ malfunction especially
in the SN, parathyroid gland, bone and gastrointestinal tract [1,2].
Vitamin D
3
Receptors (VDR) have been observed in the Substantia
Nigra (SN) [3,4]; as well as in the skin and liver of the fsh [5]. Our
choice of the VDR and VDRA, in this study, is to establish in part, the
cellular mechanism of Vitamin D
3
as a neuroprotective agent in PD
especially as it involves process formation and prevention of synaptic
denervation via signaling pathways that facilitates polymerization of
MT. Te model used for this study involved melanocytes in Ringer’s
solution containing NMDA R blocker ketamine; to induce process
and synapse-like structure formation in these cells in vitro. Tus
co-treatment, in vitro, with ketamine and Vitamin D
3
(VDRA)
describes the pharmacological action of NMDA R inhibition and VDR
potentiation. Te mechanism of the VDRA involves calcium signaling
pathways that facilitate polymerization of MT such that the αβ-tubulin
sub-units assemble and convey melanosomes and other vesicles to
the periphery of the cell using the kinesin motor assembly [6]. Tis is
believed to be complimentary to the inhibition of NMDA R; prevention
of glutamate toxicity [7], as such movement of vesicles, away from the
nucleus prevents cell death by autophagy.
Te VDRA binds to a cytoplasmic receptor VDR having two
domains; frst is the hormone binding domain and second is the DNA
binding domain. A VDR-VDRA receptor complex is formed and can
bind to the promoter region of genes, thus increasing the rate of gene
transcription and cellular activity [8]. Several studies have also shown
that VDRAs are members of neuroactive steroids capable of regulating
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ISSN: 2168-9296
Cell & Developmental Biology