title: 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.
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.
authors.affiliation: 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
authors.forename: A
authors.initials: A
authors.lastname: Barnea
authors.forename: J
authors.initials: J
authors.lastname: Roberts
authors.forename: R H
authors.initials: RH
authors.lastname: Ho
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D005333:Fetus; D005865:Gestational Age; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000096:biosynthesis; D013004:Somatostatin / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015699:HIV Envelope Protein gp120; D009478:Neuropeptide Y; D013004:Somatostatin