Use of siRNA in knocking down of dopamine receptors, a possible therapeutic option in neuropsychiatric disorders |
| |
Authors: | Mohammad-Reza Noori-Daloii Majid Mojarrad Ali Rashidi-nezhad Majid Kheirollahi Ali Shahbazi Mehdi Khaksari Asghar Korzebor Ali Goodarzi Maryam Ebrahimi Ali Reza Noori-Daloii |
| |
Institution: | (1) Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Poursina Ave, P.O.Box 14155-6447, Tehran, Iran;(2) Physiology Research Center (PRC), Tehran University of Medical Sciences, Tehran, Iran;(3) Institute for Cognitive Science Studies (ICSS), Tehran, Iran |
| |
Abstract: | Heightened dopaminergic activity has been shown to be implicated in some major neuropsychiatric disorders such as schizophrenia.
Use of dopaminergic antagonists was limited by some serious side effects related to unspecific blocking of dopamine receptors.
Thus a target specific dopamine receptor gene silencing method such as using small interfering RNA (siRNA) might be useful.
In this study recombinant plasmids expressing siRNA against dopamine receptors (D1-D5DRs) were produced, and their efficiency
in knocking down of receptors in were assessed in rat neuroblastoma cell line (B65), using Real-time PCR method. Furthermore,
D2DR siRNA expressing plasmid was injected into the rat nucleus accumbens bilaterally to investigate whether it can prevent
the hyperactivity induced by apomorphine. Locomotion was measured in 10 min intervals, 50 min before and 60 min after apomorphine
injection (0.5 mg/kg, S.C). Our results indicated that the mRNA level of dopamine receptors were reduced between 25 and 75%
in B65 cells treated with the plasmids in vitro. In behavioral tests, locomotion was lower at least in the second 10 min after
apomorphine injection in rats treated with plasmid expressing D2DR siRNA compare to control group F (4,24) = 2.77, (P < 0.05)]. The spontaneous activity of treated rats was normal. In conclusion, dopamine receptors can be downregulated by
use of siRNA expressing plasmids in nucleus accumbens. Although our work may have some possible clinical applications; the
potentially therapeutic application of siRNA in knocking down of dopamine receptors needs further studies. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|