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6th International AIDS ConferenceSan Francisco, California, USA — June 20-23, 1990 |
Int Conf AIDS 1990 Jun 20-23; 6:330 (abstract no. 1065)
Hill JM, Brenneman DE; Peptide Design L.P., Germantown, MD, USA
OBJECTIVE: In vitro studies with murine hippocampal cultures have indicated that purified HIV envelope glycoprotein, gp120, induced significant neuronal cell death which was prevented by peptide T, D-Ala peptide T amide (Brenneman et al., Nature 335,639, 1988; Drug Dev. Res. 15,361,1988). The purpose of the present study was to determine if gp120 would influence behavioral development when administered to neonatal rats, and to establish if peptide T prevented gp120-induced deficits.
METHODS: Sprague-Dawley rats received daily injections of 100 mul of one of the following: gp120 (0.3 nM), peptide T (3 muM), gp120 (0.3 nM) and peptide T (3 muM) or saline, from birth to day 14. Observations of 14 developmental milestones/behaviors were made daily without knowledge of treatment group. Statistically significant differences, as determined by ANOVA, were considered to be achieved when p less than 0.05.
RESULTS: The following developmental milestones/behaviors were significantly delayed by gp120 treatment: forelimb grasp, forelimb placement and air righting. In addition, righting reflex time was significantly delayed in the gp120-treated group. Peptide T cotreatment prevented the delay in behavioral development induced by gp120. The following developmental milestones/behaviors were not influenced by gp120 treatment: body weight, eye opening, auditory startle, crossed extensor reflex, and cliff aversion.
CONCLUSION: Systemic administration of HIV envelope glycoprotein significantly retarded the development of multiple complex motor behaviors, whereas many simple reflexes and developmental milestones were apparently unaffected. The delay in the expression of these complex motor behaviors did not occur with peptide T co-administration. These data further support the beneficial action of peptide T in preventing gp120-induced neural deficits and suggest that peptide T may be useful in the treatment of pediatric AIDS.
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