Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

Abstract

Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10 Ϫ 8 M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers.

Activity‐Dependent Neurotrophic Factor Peptide (ADNF9) Protects Neurons Against Oxidative Stress‐Induced Death

“…Injections of the same antiserum into pregnant mice inhibit CNS development, manifested in a smaller CNS at birth and apparently life‐long neurological deficits (Hill et al, 1997). In addition, developmental inhibition caused by gp 120 was prevented by treatment with ADNF (Dibbern et al, 1997).…”

Regardless of genotype, offspring of VIP‐deficient female mice exhibit developmental delays and deficits in social behavior

“…Recent studies have revealed that vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis characterized by neural tube closure and the initiation of neuronogenesis. Treatment of embryonic day 9 (E9) whole cultured mouse embryos with a dose range of VIP showed a concentration dependent and dramatic increase in growth and development over a 4 h period (Gressens et al, 1993; Dibbern et al, 1997; Hill et al, 1999; Glazner et al, 1999; Servoss et al, 2001). Treatment with the same concentration range of the related peptide, pituitary adenylate cyclase polypeptide (PACAP) had no effect at low concentrations and an inhibitory effect on growth at higher concentrations (Hill et al, 1999), illustrating the different roles of these peptides during development.…”

The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

“…Consistent with this, Brenneman et al [481] found that VIP treatment could result in the release of MIP-1α, RANTES, and chemokines to mediate the blockage of gp120 with microglial chemokine receptors. On top of this, VIP cotreatment could prevent the gp120-induced growth inhibition in mouse embryos, indicating a potential therapeutic strategy in using VIP to forestall the growth retardation as well as behavioral development experienced by infants born to HIVpositive mothers [482]. Apart from exogenous VIP application, recent case reports have also supported the putative therapeutic use of anti-VIP antibodies in AIDS management.…”