Research Article Open Access
Molecular Biomarkers & Diagnosis
Ahmadian et al., J Mol Biomark Diagn 2014, 5:3
http://10.4172/2155-9929.1000171
Volume 5 • Issue 3 • 1000171
J Mol Biomark Diagn
ISSN:2155-9929 JMBD an open access journal
*Corresponding author: Davood Zaeif, Department of Biology, Tonekabon
branch, Islamic Azad university of Tonekabon, Tonekabon, Iran, Tel:984271104;
E-mail: gene_d.zaeif@hotmail.com
Received January 31, 2014; Accepted February 19, 2014; Published February
22, 2014
Citation: Ahmadian S, Delavari G, Ghanbari D, Zaeif D (2014) D3 as a
Possible Marker Based on D1-D4 Dopamine Receptors Expression in Paranoid
Schizophrenia Patients. J Mol Biomark Diagn 5: 171. doi:10.4172/2155-
9929.1000171
Copyright: © 2014 Ahmadian S, 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: Dopamine receptors; Gene expression; Paranoid
schizophrenia; Real-time PCR
Introduction
Paranoid schizophrenia is one of several types of schizophrenia, a
chronic mental illness in which a person loses touch with reality. Te
classic features of paranoid schizophrenia are having delusions and
hearing things that aren't real. Recent progress in molecular biology
and imaging techniques has enabled new insight for schizophrenia
research, but these methods are still limited by their availability and
ofen reveal inconsistent results. Dopamine (DA) is a Catecholamine
neurotransmitter, moreover is the most abundant neurotransmitters
in CNS of animals. Dopamine, together with other catecholamine
such as norepinephrine, is also a critical transmitter in sympato
adrenergic terminals. Such terminals lie in close contact with immune
cells in lymphoid organs and there is increasing evidence which
points to the ability of dopamine to afect immune cell function [1].
Dopamine receptors are integral membrane proteins that interact
with G proteins to transduce dopamine stimulation into intracellular
responses. Dopaminergic neurons in the human central nervous
system are involved in the control of motor activity and in emotional
and cognitive processes [2]. Te human genome is known to contain
fve genes encoding the functional dopamine receptors, DRD1,
DRD2, DRD3, DRD4, DRD5 and two genes highly homologous to
the DRD5 encoding the pseudogenes [3-5]. Te expression of the
dopamine receptors is well characterized in the brain but little work has
been done to examine the expression in other tissue organs. Human
Peripheral Blood Lymphocytes (PBL) expresses dopamine receptors
and dopamine transporters and synthesizes endogenous dopamine and
the related catecholamine norepinephrine and epinephrine through
tyrosine hydroxylase dependent pathway [5]. Interestingly, dysfunction
of dopaminergic pathways in PBL has been reported in neurological
disorders characterized by dysfunctional central dopaminergic
neurotransmission such as peripheral dopaminergic [6].
Although, it is yet unclear whether they simply mirror dysfunctional
dopaminergic mechanisms or primarily refect a dynamic interaction
between the central nervous system and circulating immune cells. It has
been proposed that neurotransmitter expression in peripheral immune
cells refects expression of these receptors in the brain. Te purposes
of this study were to examine if the mRNA of peripheral dopamine
receptor is statically changed in paranoid schizophrenia, and whether
or not these receptors have some value as a potential peripheral marker
refecting central one in paranoid schizophrenia.
Materials and Methods
Study design
Te total number of subjects was 87 paranoid schizophrenia
patients. 22 of them were chronic who had been taking antipsychotic
drugs for more than 3 years (drug-med patients), 15 were drug-
free who had not taken antipsychotic drugs for more than 3 months
(drug-free patients), and 5 were drug-naïve who had never taken
antipsychotic drugs (drug-naïve patients). For the controls, age and
sex matched 20 healthy persons were enrolled. All patients fulflled the
DSM-IV criteria and the patients with a previous history of neurologic,
neuropsychologic, medical, and surgical disease were excluded.
Quantitation of dopamine receptor RNA
Preparation of blood lymphocyte: 2 ml of peripheral blood samples
were placed in 200 µl EDTA 0.05M falcon gradients and centrifuged
in 2500 rpm for 20minutes. Upper layer moved in new falcon and
washed by v/v PBS; then centrifuged in 1500 rpm for 10 minutes for
two times. Separation of lymphocytes did not done laterthan one hour
afer drawing blood [7].
D3 as a Possible Marker Based on D1-D4 Dopamine Receptors Expression
in Paranoid Schizophrenia Patients
Sorour Ahmadian
1
, Ghazal Delavari
2
, Donya Ghanbari
2
and Davood Zaeif
1
*
1
Department of Biology, Tonekabon branch, Islamic Azad university of Tonekabon,Tonekabon, Iran
2
Institute of Molecular diagnostic and Microbial research center of BioBarcode, Tehran, Iran
Abstract
Paranoid schizophrenia is one of several types of schizophrenia, a chronic mental illness in which a person loses
touch with reality. The classic features of paranoid schizophrenia are having delusions and hearing things that aren’t
real. Based on Numerous studies about dopamine and schizophrenia, it suggested that changes in the dopamine
systems are in related with schizophrenia, but still there is no clear direct evidence for dopamine hypothesis in
schizophrenia.
In terminated examination, 20 paranoid schizophrenia patients mRNA from white blood cells extracted, then
cDNA were synthesized. After Quantitive Real-time PCR examination with the related primaries for D1-D4 receptors
were terminated and the compared consequences in abundance of genes expression with the normal samples
reveal that D1-D4 dopamine receptors were expressed in all samples. Abundance of normal individuals were D1
100%, D2 6.6%, D3 40%, D4 86.6% and for patients were D1 100%, D2 26.6%, D3 33.3%, D4 73.3%. The results of
this study reveals signifcant differences between D3 receptor apply to others. Therefore D3 has a possible clinical
signifcance for using as rapid diagnosis of people who suspicious of paranoid schizophrenia.