Reiner Benjamin, Wang Wenwei, Liu Jianuo, Xiong Huangui
The Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA; Department of Biology, West Chester University of Pennsylvania, West Chester, PA 19383, USA.
The Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA; Department of Physiology, Fudan University School of Medicine, Shanghai, China.
Neurosci Lett. 2016 Feb 26;615:83-7. doi: 10.1016/j.neulet.2016.01.033. Epub 2016 Jan 22.
It is well established that HIV-1-infected mononuclear phagocytes release platelet activating factor (PAF) and elevated levels of PAF have been detected in blood and in the cerebrospinal fluid (CSF) of acquired immunodeficiency syndrome (AIDS) patients with HIV-associated neurocognitive disorders (HAND). It is our hypothesis that the elevated levels of PAF alter long-term potentiation (LTP) in the hippocampus, leading to neurocognitive dysfunction. To test this hypothesis, we studied the effects of PAF on LTP in the CA1 region of rat hippocampal slices. Our results showed incubation of hippocampal slices with PAF attenuated LTP. The PAF-mediated attenuation was blocked by ginkgolide B, a PAF receptor antagonist, suggesting PAF attenuation of LTP via PAF receptors. Application of lyso-PAF, an inactive PAF analog, had no apparent effect on LTP. Further investigation revealed an involvement of tyrosine kinase in PAF attenuation of LTP, which was demonstrated by lavendustin A (a specific protein tyrosine kinase inhibitor) blockage of PAF attenuation of LTP. As LTP is widely considered as the cellular and synaptic basis for learning and memory, the attenuation of LTP by PAF may contribute at least in part to the HAND pathogenesis.
众所周知，感染HIV-1的单核吞噬细胞会释放血小板活化因子（PAF），并且在患有HIV相关神经认知障碍（HAND）的获得性免疫缺陷综合征（AIDS）患者的血液和脑脊液（CSF）中已检测到PAF水平升高。我们的假设是，PAF水平升高会改变海马体中的长时程增强（LTP），导致神经认知功能障碍。为了验证这一假设，我们研究了PAF对大鼠海马切片CA1区LTP的影响。我们的结果表明，用PAF孵育海马切片会减弱LTP。PAF受体拮抗剂银杏内酯B可阻断PAF介导的减弱作用，表明PAF通过PAF受体减弱LTP。应用无活性的PAF类似物溶血PAF对LTP没有明显影响。进一步的研究表明，酪氨酸激酶参与了PAF对LTP的减弱作用，这一点通过lavendustin A（一种特异性蛋白酪氨酸激酶抑制剂）阻断PAF对LTP的减弱作用得到了证明。由于LTP被广泛认为是学习和记忆的细胞和突触基础，PAF对LTP的减弱可能至少部分导致了HAND的发病机制。
