Delayed developmental changes in neonatal vocalizations correlates with variations in ventral medial hypothalamus and central amygdala development in the rodent infant: effects of prenatal cocaine.

While variations in neonatal distress vocalizations have long been shown to reflect the integrity of nervous system development following a wide range of prenatal and perinatal insults, a paucity of research has explored the neurobiological basis of these variations. To address this, virgin Sprague-Dawley rats were bred and divided into three groups: [1] untreated, [2] chronic-cocaine treated (30 mg/kg/day, gestation days (GDs) 1-20); or [3] chronic saline treated (2 mg/kg/day, GDs 1-20). Pregnant dams were injected with Bromodeoxyuridine (10 mg/kg) on GDs 13-15 to label proliferating cells in limbic regions of interest. Ultrasonic vocalizations (USVs) were recorded on postnatal days (PNDs) 1, 14, and 21, from one male and female pup per litter. Variations in acoustic properties of USVs following cocaine-exposure were age and sex-dependent including measures of total number, total duration and amplitude of USVs, and percent of USVs with at least one harmonic. Following USV testing brains were stained with standard fluorescent immunohistochemistry protocols and examined for variations in neuronal development and if variations were associated with acoustic characteristics. Limbic region developmental differences following cocaine-exposure were sex- and age-dependent with variations in the ventral medial hypothalamus and central amygdala correlating with variations in vocalizations on PND 14 and 21. Results suggest maturation of the ventral medial hypothalamus and central amygdala may provide the basis for variations in the sound and production of USVs. As vocalizations may serve as a neurobehavioral marker for nervous system integrity, understanding the neurobiological basis of neonatal vocalizations may provide the basis for early intervention strategies in high-risk infant populations.

The gp120 envelope of HIV-1 binds peptides in a similar manner to human leukocyte antigens.

OBJECTIVE: All the conserved regions of HIV gp120 have at least some partial homology with human leukocyte antigen (HLA) class I or class II. One functional similarity is the ability of gp120 and HLA class II to bind CD4. Given the close association between HIV-induced disease and the amount of immune activation and anergy, features closely associated with chronic allogenic stimulation, we asked whether gp120 shared any other properties of HLA, in this case the ability to bind peptides. DESIGN: T-cell epitope peptides known to bind to soluble HLA class I or class II were photolabelled and made radioactive. Cross-linking of modified peptides to soluble HLA class I, II and gp120 was activated by ultraviolet light and analysed by sodium dodecylsulphate-polyacrylamide gel electrophoresis. RESULTS: A signal peptide binding to HLA class I and a haemagglutinin peptide that binds to HLA class II were found to bind soluble gp120 specifically; binding and cross-linking could be competed out with excess of the unmodified peptides but not unrelated control peptides. Molecular modelling of gp120 suggests shared anchor sites for peptides binding to both HLA and gp120 soluble molecules. CONCLUSIONS: The ability to bind these two peptides suggests that gp120 has a peptide-binding site of broad specificity, which if functional in vivo, could compete with normal peptide loading of major histocompatibility complex (MHC) class I and/or class II peptides, as well as aberrantly stimulate the T-cell receptor (by virtue of its potential to be mistaken for an allogenic MHC/peptide complex), resulting in immune activation, anergy and apoptosis in susceptible hosts.