title: Astrocytic expression of HIV-1 viral protein R in the hippocampus causes chromatolysis, synaptic loss and memory impairment.
abstract: BACKGROUND
  HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cell death of cultured rat hippocampal neurons and suppresses axonal growth. Behavioral studies are limited and suggest hyperactivity in the presence of Vpr. Thus Vpr may play a role in hippocampal loss of function. The purpose of this study is to determine the ability of HIV-1 Vpr production by astrocytes in the hippocampus to cause neurological deficits and memory impairments.
  
  
  METHODS
  We tested the performance of rats in novel object and novel location tasks after hippocampal infusion with astrocytes expressing HIV-1 Vpr. Synaptic injury and morphological changes were measured by synaptophysin immunoreactivity and Nissl staining.
  
  
  RESULTS
  Vpr-infused rats showed impaired novel location and novel object recognition compared with control rats expressing green fluorescent protein (GFP). This impairment was correlated with a significant decrease in synaptophysin immunoreactivity in the hippocampal CA3 region, suggesting synaptic injury in HIV-1 Vpr-treated animals. In addition, Nissl staining showed morphological changes indicative of neuronal chromatolysis in the Vpr group. The Vpr-induced neuronal damage and synaptic loss suggest that neuronal dysfunction caused the spatial and recognition memory deficits found in the Vpr-infused animals.
  
  
  CONCLUSIONS
  In this study, we demonstrate that HIV-1 Vpr produced by astrocytes in the hippocampus impairs hippocampal-dependent learning. The data suggest Vpr is a neurotoxin with the potential to cause learning impairment in HIV-1 infected individuals even under conditions of limited viral replication.
authors.forename: Lilith
authors.initials: L
authors.lastname: Torres
authors.affiliation: Department of Biochemistry, Ponce School of Medicine and Health Sciences, P,O Box 7004, 00731 Ponce, PR, USA. rnoel@psm.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Noel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception; D013569:Synapses / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016708:Synaptophysin; C569016:Syp protein, rat; D054325:vpr Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins