Central nervous system expression of HIV-1 gp120 activates the hypothalamic-pituitary-adrenal axis: Evidence for involvement of NMDA receptors and nitric oxide synthase

Jacob Raber, Stephanie M. Toggas, Sherina Lee, Floyd E. Bloom, Charles J. Epstein, Lennart Mucke

Research output: Contribution to journalArticle

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Abstract

The impact of HIV-1 expression in the brain on the development of AIDS is unknown. In the present study, we examined the hypothalamic-pituitary-adrenal (HPA) axis in a transgenic model in which expression of the HIV-1 envelope glycoprotein gp120 induced central nervous system (CNS) damage similar to that seen in HIV-1-infected patients. Compared with nontransgenic littermates, gp120 transgenic mice showed significant increases in plasma corticosterone and adrenocorticotrophic hormone (ACTH) levels and pituitary ACTH content. To determine whether this activation of the HPA axis could be mediated by ACTH secretagogues, the effect of recombinant gp120 on the release of these factors from hypothalamic slices was investigated in vitro. Recombinant gp120 induced release of the ACTH secretagogue arginine vasopressin from nontransgenic hypothalamic slices in a calcium-dependent fashion. This effect was inhibited by antagonists of N-methyl-D-aspartate (NMDA) receptors or of nitric oxide synthase (NOS), suggesting a role for NMDA receptor stimulation and NOS activity. Further evidence for a role of free radicals was obtained from bigenic mice coexpressing gp120 and the free radical scavenger human copper/zinc superoxide dismutase which showed normal corticosterone levels. This might relate to superoxide dismutase-mediated scavenging of superoxides generated by NOS. These findings demonstrate that CNS expression of a viral envelope protein can activate the HPA axis and thereby alter peripheral levels of immunomodulatory hormones.

Original languageEnglish (US)
Pages (from-to)362-373
Number of pages12
JournalVirology
Volume226
Issue number2
DOIs
StatePublished - Dec 15 1996
Externally publishedYes

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N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
Adrenocorticotropic Hormone
HIV-1
Central Nervous System
Corticosterone
Superoxide Dismutase
HIV Envelope Protein gp120
Viral Envelope Proteins
Free Radical Scavengers
Pituitary Hormones
Arginine Vasopressin
Superoxides
Transgenic Mice
Free Radicals
Zinc
Copper
Acquired Immunodeficiency Syndrome
Hormones
Calcium

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Central nervous system expression of HIV-1 gp120 activates the hypothalamic-pituitary-adrenal axis : Evidence for involvement of NMDA receptors and nitric oxide synthase. / Raber, Jacob; Toggas, Stephanie M.; Lee, Sherina; Bloom, Floyd E.; Epstein, Charles J.; Mucke, Lennart.

In: Virology, Vol. 226, No. 2, 15.12.1996, p. 362-373.

Research output: Contribution to journalArticle

Raber, Jacob ; Toggas, Stephanie M. ; Lee, Sherina ; Bloom, Floyd E. ; Epstein, Charles J. ; Mucke, Lennart. / Central nervous system expression of HIV-1 gp120 activates the hypothalamic-pituitary-adrenal axis : Evidence for involvement of NMDA receptors and nitric oxide synthase. In: Virology. 1996 ; Vol. 226, No. 2. pp. 362-373.
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