Namjoo Elham, Shekari Mohammad, Piruozi Aliyar, Forouzandeh Hossein, Khalafkhany Davod, Vahedi Abdolvahid, Ahmadi Iraj
Department of Biology, Faculty of Science, Arsenjan Branch, Islamic Azad University, Fars, Iran.
Genetics and Molecular Biology, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Basic Clin Neurosci. 2020 Jan-Feb;11(1):49-58. doi: 10.32598/bcn.11.1.1272.1. Epub 2020 Jan 1.
Microglia, small glial cells, i.e. mesodermal in origin and found in the brain and spinal cord, play a key role in the maintenance of neurons and immune defense. Haloperidol, an antipsychotic drug, is used to treat numerous neurological and neurodegenerative disorders. Its mechanism is not understood; however, haloperidol may result in Wnt signaling pathway activation. This study aimed to activate the Wnt signaling pathway using haloperidol and determining the effect of GSK3 inhibition on the expression of TGFB, NT-3, and BDNF genes in cultured rat microglia.
Microglia isolation was conducted, and the immunohistochemistry technique was performed to confirm microglia purity. The RNA extraction was followed by cDNA synthesis. Real-time RT-PCR was used to evaluate any significant changes in the expression level of these genes.
The three gene expressions in microglia were proportional to the different concentrations of the drug. More concentration of drugs resulted in higher levels of expression of these genes. Besides, the haloperidol did not affect the expression of the beta-actin gene as the reference gene.
The obtained results supported the beneficial use of haloperidol in targeted microglia therapy. This study can be a breakthrough in neurology research.
小胶质细胞是一种起源于中胚层的小型神经胶质细胞，存在于脑和脊髓中，在维持神经元和免疫防御方面发挥着关键作用。氟哌啶醇是一种抗精神病药物，用于治疗多种神经和神经退行性疾病。其作用机制尚不清楚；然而，氟哌啶醇可能会导致Wnt信号通路激活。本研究旨在使用氟哌啶醇激活Wnt信号通路，并确定抑制糖原合成酶激酶3（GSK3）对培养的大鼠小胶质细胞中转化生长因子β（TGFB）、神经营养因子3（NT-3）和脑源性神经营养因子（BDNF）基因表达的影响。
进行小胶质细胞分离，并采用免疫组织化学技术确认小胶质细胞的纯度。随后进行RNA提取和cDNA合成。采用实时逆转录聚合酶链反应（Real-time RT-PCR）评估这些基因表达水平的任何显著变化。
小胶质细胞中这三种基因的表达与药物的不同浓度成正比。药物浓度越高，这些基因的表达水平越高。此外，氟哌啶醇作为参照基因，不影响β-肌动蛋白基因的表达。
所得结果支持氟哌啶醇在靶向小胶质细胞治疗中的有益应用。本研究可能成为神经学研究的一个突破。
