Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Brain Res. 1999 Jan 9;815(2):349-57. Unique Identifier : AIDSLINE MED/99096587
Barnea A; Roberts J; Ho RH; Department of Obstetrics and Gynecology, The University of Texas; Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd.,; Dallas, TX 75235-9032, USA. abarn1@mednet.swmed.edu

Abstract: Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalitis. Since gp120 is thought to play a major role in AIDS-associated abnormalities in the brain, we addressed the question: Does gp120 alter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-age dependent? Aggregate cultures, obtained from cortices of nine fetuses (14.9-20.7 weeks), were exposed for 7 days to BDNF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed. Similar effects of BDNF and gp120 were observed in the 9 brain-cultures. A 7-day exposure to BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alone did not. Co-exposure to BDNF and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than that after BDNF alone (p=0.006). These effects were BDNF- and gp120-dose dependent and they were not accompanied by changes in DNA content of the aggregates nor in lactate dehydrogenase activity in the medium; indicating that gp120 did not lead to a major loss of cell integrity. These results are consistent with a synergistic effect of BDNF and gp120 leading to enhanced functional expression of the signalling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains throughout the 2nd trimester of gestation. Thus, this culture system can serve as a model to study the mechanism(s) underlying the early interactions between gp120 BDNF in the developing human brain. Copyright 1999 Elsevier Science B.V.

Keywords: JOURNAL ARTICLE Brain-Derived Neurotrophic Factor/*PHARMACOLOGY Cells, Cultured Cerebral Cortex/CYTOLOGY/DRUG EFFECTS/*METABOLISM Drug Synergism Fetus Gestational Age Human HIV Envelope Protein gp120/*PHARMACOLOGY Neurons/DRUG EFFECTS/*METABOLISM Neuropeptide Y/BIOSYNTHESIS Somatostatin/*BIOSYNTHESIS/METABOLISM Support, U.S. Gov't, P.H.S.
990530
A9950945

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