Establishment of a rodent model of HIV-associated sensory neuropathy

Sanjay C. Keswani, Christelene Jack, Chunhua Zhou, Ahmet Hoke

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most common neurological complication of HIV infection in the current highly active antiretroviral therapy era. The painful sensory neuropathy is associated with the use of dideoxynucleoside antiretrovirals, and its development limits the choice of antiretroviral drugs in affected patients. There are presently no effective therapies for HIV-SN, and moreover there has been no robust animal model of HIV-SN in which candidate therapeutic agents can be tested. In this paper, we show that we have established a rodent model of HIV-SN by oral administration of a dideoxynucleoside drug, didanosine, to transgenic mice expressing the HIV coat protein gp120 under a GFAP promoter. The neuropathy in these rodents is characterized by distal degeneration of unmyelinated sensory axons, similar to the "dying back" pattern of C-fiber loss seen in patients with HIV-SN. This model will be useful in examining mechanisms of distal axonal degeneration and testing potential neuroprotective compounds that may prevent development of the sensory neuropathy.

Original languageEnglish (US)
Pages (from-to)10299-10304
Number of pages6
JournalJournal of Neuroscience
Volume26
Issue number40
DOIs
StatePublished - Oct 4 2006

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Rodentia
HIV
Dideoxynucleosides
Didanosine
Human Immunodeficiency Virus Proteins
Unmyelinated Nerve Fibers
Highly Active Antiretroviral Therapy
Capsid Proteins
Virus Diseases
Pharmaceutical Preparations
Transgenic Mice
Oral Administration
Axons
Animal Models
Therapeutics

Keywords

  • Animal model
  • DDI
  • Dideoxynucleoside
  • gp120
  • HIV
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Establishment of a rodent model of HIV-associated sensory neuropathy. / Keswani, Sanjay C.; Jack, Christelene; Zhou, Chunhua; Hoke, Ahmet.

In: Journal of Neuroscience, Vol. 26, No. 40, 04.10.2006, p. 10299-10304.

Research output: Contribution to journalArticle

Keswani, Sanjay C. ; Jack, Christelene ; Zhou, Chunhua ; Hoke, Ahmet. / Establishment of a rodent model of HIV-associated sensory neuropathy. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 40. pp. 10299-10304.
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