Neonatal intrahippocampal gp120 injection: An examination early in development

• Published in: Neurotoxicology (Park Forest South) Vol. 28; no. 1; pp. 101 - 107
• Main Authors: Fitting, Sylvia, Booze, Rosemarie M., Mactutus, Charles F.
• Format: Journal Article
• Language: English
• Published: Orlando, FL Elsevier B.V 01.01.2007; Elsevier
• Subjects: Animals; Animals, Newborn - physiology; Behavior, Animal - drug effects; Biological and medical sciences; Body Weight - drug effects; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Female; Gp120; Hippocampus; Hippocampus - drug effects; Hippocampus - growth & development; HIV Envelope Protein gp120 - administration & dosage; HIV Envelope Protein gp120 - pharmacology; HIV-1; Human immunodeficiency virus 1; Human viral diseases; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Injections; Male; Medical sciences; Postural Balance - drug effects; Preattentive processes; Pregnancy; Prepulse inhibition; Psychomotor Performance - drug effects; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Reflex, Startle - drug effects; Sensory-motor system; Toxicology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; HIV-1; Sensory-motor system; Gp120; Preattentive processes; Hippocampus; Prepulse inhibition; Immunopathology; Neonatal; HIV-1 virus; Central nervous system; Retroviridae; AIDS; Injection; Immune deficiency; Lentivirus; Encephalon; Infection; Virus; Viral disease; Development; Early; Inhibitor; Human immunodeficiency virus; Inhibition; Gpl20
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2006.07.014

The presence of human immunodeficiency virus type 1 (HIV-1) in the brain is believed to be responsible for mediating the pathogenesis of neurological abnormalities through the viral toxins gp120 and Tat. Numerous studies indicate neurotoxic effects of the HIV-1-protein Tat, with demonstrated neurobehavioral and cognitive alterations. However, less clear is the neurotoxic effect of gp120 on neurobehavior. This study was designed to characterize the potential deficits in sensory-motor and preattentive functions, following intrahippocampal administration of gp120. Using a randomized-block design, male and female pups of eight Sprague–Dawley litters were injected bilaterally with either vehicle (VEH) (1 μl volume) or one of the three gp120 doses (1.29, 12.9, or 129 ng/μl) at postnatal day (P)1. Sensory-motor functions were assessed at P3, as measured by the righting reflex and at P8, as measured by negative geotaxis. At P24 animals were tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by prepulse inhibition (PPI) of the auditory startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin-square design). Results indicated gp120-induced neurotoxicity on the righting reflex but not negative geotaxis. For sensorimotor gating, the PPI test demonstrated a reduced inhibition response on peak ASR latency as the dose of gp120 increased. No effect was noted for response inhibition on peak ASR amplitude. These data suggest that intrahippocampal injection of gp120 (0, 1.29, 12.9, or 129 ng/μl) had transient neurotoxic effects on sensory-motor function and limited effects on preattentive processes early in development.