title: Platelet-activating factor attenuation of long-term potentiation in rat hippocampal slices via protein tyrosine kinase signaling.
abstract: 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.
authors.affiliation: 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Reiner
authors.affiliation: 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.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Jianuo
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. Electronic address: hxiong@unmc.edu.
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D010972:Platelet Activating Factor; D011505:Protein-Tyrosine Kinases
keywords: HIV; HIV-associated dementia; Hippocampal slice; LTP; Platelet activating factor