Durham Research Center, Room 8013
985880 Nebraska Medical Center
Omaha, NE 68198-5880
E-mail: Huangui Xiong
Keywords: voltage-gated K channels, NMDA receptors, synaptic transmission and plasticity, neuroinflammation, neuromodulation, learning and memory, HIV-1-associated neurological disorders
The research in my laboratory investigates how HIV-1 brain infection causes neuronal and synaptic damage leading to the pathogenesis of HIV-1-associated neurocognitive disorder (HAND), a neurological complication with relatively high incidence even in the era of combined antiretroviral therapy. Specifically, we are interested in studying how HIV-1-infected and/or immune-activated mononuclear phagocytes (MPs, brain macrophages and microglia) impair neuronal function, synaptic transmission and plasticity in the hippocampus (a brain region widely believed to be involved in learning and memory) with a particular focus on how soluble viral (e.g., Tat, gp120) and cellular (e.g., cytokines and chemokines) factors, secreted by HIV-1-infected and/or immune-activated MPs, impair neuronal and synaptic physiology via alteration of synaptic and extra-synaptic NMDA receptor function leading to neuronal and synaptic dysfunction/injury and ultimate HAND pathogenesis . We are also interested in studying voltage-gated K+ (Kv) channels in the regulation of MP activation, resultant production of neurotoxins and consequent neurotoxic activity both in vitro and in vivo, focusing on Kv1.3 and Kv2.1. We anticipate that experimental results generated from these studies may help us not only understand the mechanisms underlying HAND pathogenesis, but also identify specific target(s) for the development of therapeutic strategies.
The goals of our laboratory are:
- To determine and characterize the role played by voltage-gated K+ channels in the pathogenesis of HIV-1-associated Neurocognitive Disorders (HAND) and identify potential targets for the development of therapeutic strategies.
- To examine and clarify the involvement of synaptic NR2A receptors and extra-synaptic NR2B receptors in HAND pathogenesis and explore therapeutic potential of specific antagonists both in vitro and in vivo.
Ton H, Xiong H. (2013) Astrocyte Dysfunctions and HIV-1 Neurotoxicity. J AIDS Clin Res 4(11): 255. PMID: 24587966
Liu H, Liu J, Liang S, Xiong H. (2013) Plasma gelsolin protects HIV-1 gp120-Induced neuronal injury via voltage-gated K+ channel Kv2.1. Mol Cell Neurosci S1044-7431(13): 00101-2. PMID: 24513395
Xiong W, Xie J, Liu J, Xiong H. (2014) [HIV-1gp120 injures neurons by alteration of neuronal expressions of NR2B and PSD-95]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30(2): 139-42. PMID: 24491052
Del Debbio CB, Peng X, Xiong H, Ahmad I. (2013) Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences. BMC Neurosci 14: 130. PMID: 24148749
Xia J, Xiong H. (2013) Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine. Int J Physiol Pathophysiol Pharmacol 5(3): 137-47. PMID: 24044033
Haorah J, Rump TJ, Xiong H. (2013) Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration. PLoS One 8(8): e70833. PMID: 23967116
Liu J, Xu P, Collins C, Liu H, Zhang J, Keblesh JP, Xiong H. (2013) HIV-1 Tat protein increases microglial outward K(+) current and resultant neurotoxic activity. PLoS One 8(5): e64904. PMID: 23738010
Yang J, Hu D, Xia J, Liu J, Zhang G, Gendelman HE, Boukli NM, Xiong H. (2013) Enhancement of NMDA receptor-mediated excitatory postsynaptic currents by gp120-treated macrophages: implications for HIV-1-associated neuropathology. J Neuroimmune Pharmacol 8(4): 921-33. PMID: 23660833
Martinez-Skinner AL, Veerubhotla RS, Liu H, Xiong H, Yu F, McMillan JM, Gendelman HE. (2013) Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity. J Proteome Res 12(5): 2282-94. PMID: 23544708
Zhang J, Liu J, Fox HS, Xiong H. (2013) N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum. J Neurosci Res 91(2): 240-8. PMID: 23161705