Infection with the HIV-1 virus is associated with effects on both the central and peripheral nervous systems including the HIV-1 cognitive/motor syndrome and HIV-1 -related sensory neuropathies. In this grant proposal we shall investigate the mechanisms by which the HIV-1 virus can compromise the function of sensory neurons associated with pain. In our preliminary data we demonstrate that sensory (dorsal root ganglion, [DRG]) neurons express the CXCR4 as well as other chemokine receptors. Activation of these receptors by chemokines or by the HIV-1 coat protein gpl20 activates intracellular signaling pathways that produce neuronal excitation and pain. Gp120 also activates the JNK signaling pathway that ultimately produces neuronal apoptotic death. In the experiments discussed in this proposal we shall (1) further examine the role of the CXCR4 and other receptors in mediating the effects of gp120 on DRG neurons; (2) examine the interactions between chemokines, gpl20, anti-retroviral drugs and members of the JNK signaling pathway in compromising the function of sensory neurons; and (3) examine the mechanisms by which gpl20 produces activation of JNK and induces the death of DRG neurons. These results will help us to understand how the HIV-1 virus can compromise the functions of sensory neurons and suggest novel targets for therapeutic interventions in the treatment of HIV-1 -associated sensory neuropathies.
| Belmadani, Abdelhak; Ren, Dongjun; Bhattacharyya, Bula J et al. (2015) Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF-1. Hippocampus 25:1224-41 |
| Bhattacharyya, Bula J; Wilson, Scott M; Jung, Hosung et al. (2012) Altered neurotransmitter release machinery in mice deficient for the deubiquitinating enzyme Usp14. Am J Physiol Cell Physiol 302:C698-708 |
| Banisadr, Ghazal; Bhattacharyya, Bula J; Belmadani, Abdelhak et al. (2011) The chemokine BRAK/CXCL14 regulates synaptic transmission in the adult mouse dentate gyrus stem cell niche. J Neurochem 119:1173-82 |
| Wilson, Natalie M; Jung, Hosung; Ripsch, Matthew S et al. (2011) CXCR4 signaling mediates morphine-induced tactile hyperalgesia. Brain Behav Immun 25:565-73 |
| White, Fletcher; Wilson, Natalie (2010) Opiate-induced hypernociception and chemokine receptors. Neuropharmacology 58:35-7 |
| White, Fletcher A; Miller, Richard J (2010) Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain. Brain Behav Immun 24:859-65 |
| Bhangoo, Sonia K; Ripsch, Matthew S; Buchanan, David J et al. (2009) Increased chemokine signaling in a model of HIV1-associated peripheral neuropathy. Mol Pain 5:48 |
| Abbadie, Catherine; Bhangoo, Sonia; De Koninck, Yves et al. (2009) Chemokines and pain mechanisms. Brain Res Rev 60:125-34 |
| White, Fletcher A; Feldman, Polina; Miller, Richard J (2009) Chemokine signaling and the management of neuropathic pain. Mol Interv 9:188-95 |
| Miller, Richard J; Jung, Hosung; Bhangoo, Sonia K et al. (2009) Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol :417-49 |
Showing the most recent 10 out of 26 publications
