title: Reduction of pyramidal and immature hippocampal neurons in pediatric simian immunodeficiency virus infection.
abstract: Pediatric HIV infection remains a global health crisis with a worldwide infection rate of 2.5 million (WHO, Geneva Switzerland, 2009). Children are much more susceptible to HIV-1 neurological impairments compared with adults, which is exacerbated by coinfections. A major obstacle in pediatric HIV research is sample access. The proposed studies take advantage of ongoing pediatric simian immunodeficiency virus (SIV) pathogenesis and vaccine studies to test the hypothesis that pediatric SIV infection diminishes neuronal populations and neurogenesis in the hippocampus. Newborn rhesus macaques (Macaca mulatta) that received intravenous inoculation of highly virulent SIVmac251 (n=3) or vehicle (control n=4) were used in this study. After a 6-18-week survival time, the animals were euthanized and the brains prepared for quantitative histopathological analysis. Systematic sections through the hippocampus were either Nissl stained or immunostained for doublecortin (DCX+), a putative marker of immature neurons. Using design-based stereology, we report a 42% reduction in the pyramidal neuron population of the CA1, CA2, and CA3 fields of the hippocampus (P<0.05) in SIV-infected infants. The DCX+ neuronal population was also significantly reduced within the dentate gyrus of the hippocampus. The loss of hippocampal neurons and neurogenic capacity may contribute to the rapid neurocognitive decline associated with pediatric HIV infection. These data suggest that pediatric SIV infection, which leads to significant neuronal loss in the hippocampus within 3 months, closely models a subset of pediatric HIV infections with rapid progression.
authors.affiliation: Departments of aPhysiology and Biophysics bPsychiatry, College of Medicine, Howard University cDepertment of Anatomy, Howard University School of Medicine, Washington, District of Columbia dCalifornia National Primate Research Center, University of California Davis, Davis, California eDepartment of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Curtis
authors.forename: Matthew
authors.initials: M
authors.lastname: Rollins
authors.forename: Heather
authors.initials: H
authors.lastname: Carryl
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bradshaw
authors.forename: Bradshaw
authors.initials: B
authors.lastname: Kimberley
authors.forename: Koen K A
authors.initials: KK
authors.lastname: Van Rompay
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
authors.forename: Mark W
authors.initials: MW
authors.lastname: Burke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000089622:Doublecortin Domain Proteins; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology*; D015302:Simian Immunodeficiency Virus
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
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