Heshmati-Fakhr Nooshin, Sotoodehnejadnematalahi Fattah, Yousefi Niloufar, Sayyah Mohammad, Hosseini Sayed Masoud, Pourbadie Hamid Gholami
Department of Physiology and Pharmacology, Pasteur Institute of Iran.
Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University.
Neuroreport. 2018 Dec 5;29(17):1456-1462. doi: 10.1097/WNR.0000000000001132.
Synaptic function and memory performance are disrupted by soluble form of β-amyloid (Aβ). In the previous study, we found that early activation of microglia by toll-like receptor 2 (TLR2) attenuated Alzheimer's disease-associated cognitive deficit. This study was designed to investigate whether pretreatment with the TLR2 receptor ligand can regulate microglia to produce interferon β (INFβ) in a rat model of Alzheimer's disease. For this purpose, the BV-2 cell line was cultured in a 24-well plate, treated with Pam3Cys (1 μg/ml), and then incubated with oligomeric Aβ for 24 h. The expression of TRIF, IRF3, and INFβ was measured by western blot technique. For in-vivo study, bilateral guide cannulas were streotaxically implanted in the right and left lateral ventricles. Pam3Cys/vehicle was microinjected into the right ventricle every 3 days. Two weeks later, an osmotic pump was inserted into the left ventricle to microinfuse oligomeric Aβ/placebo over 14 days. In the meanwhile, treatment with Pam3Cys was continued every 3 days. Then, expression of TRIF, IRF3, and INFβ was measured in the hippocampus. The results showed that although oligomeric Aβ could not alter the expression of these proteins at the cell and tissue level, treatment with Pam3Cys resulted in enhanced expression of them at both cell culture and hippocampal tissue following treatment with oligomeric Aβ. It is concluded that stimulation of microglia through TLR2 pathway induces INFβ expression, which may in part mediate neuroprotection against oligomeric Aβ.
β-淀粉样蛋白（Aβ）的可溶性形式会破坏突触功能和记忆表现。在先前的研究中，我们发现Toll样受体2（TLR2）早期激活小胶质细胞可减轻阿尔茨海默病相关的认知缺陷。本研究旨在调查在阿尔茨海默病大鼠模型中，用TLR2受体配体进行预处理是否能调节小胶质细胞产生干扰素β（INFβ）。为此，将BV-2细胞系培养在24孔板中，用Pam3Cys（1μg/ml）处理，然后与寡聚Aβ孵育24小时。通过蛋白质印迹技术测量TRIF、IRF3和INFβ的表达。对于体内研究，将双侧引导套管立体定向植入左右侧脑室。每3天向右侧脑室微量注射Pam3Cys/赋形剂。两周后，将渗透泵插入左侧脑室，在14天内微量注入寡聚Aβ/安慰剂。同时，每3天继续用Pam3Cys治疗。然后，测量海马体中TRIF、IRF3和INFβ的表达。结果表明，虽然寡聚Aβ在细胞和组织水平上不会改变这些蛋白质的表达，但在用寡聚Aβ处理后，Pam3Cys处理导致细胞培养和海马组织中它们的表达增强。得出的结论是，通过TLR2途径刺激小胶质细胞可诱导INFβ表达，这可能部分介导对寡聚Aβ的神经保护作用。
