title: Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala.
abstract: Human immunodeficiency virus type 1 (HIV) infection of the brain produces cognitive and motor disorders. In addition, HIV positive individuals exhibit behavioral alterations, such as apathy, and a decrease in spontaneity or emotional responses, typically seen in anxiety disorders. Anxiety can lead to psychological stress, which has been shown to influence HIV disease progression. These considerations underscore the importance of determining if anxiety in HIV is purely psychosocial, or if by contrast, there are the molecular cascades associated directly with HIV infection that may mediate anxiety. The present study had two goals: (1) to determine if chronic exposure to viral proteins would induce anxiety-like behavior in an animal model and (2) to determine if this exposure results in anatomical abnormalities that could explain increased anxiety. We have used gp120 transgenic mice, which display behavior and molecular deficiencies similar to HIV positive subjects with cognitive and motor impairments. In comparison to wild type mice, 6 months old gp120 transgenic mice demonstrated an anxiety like behavior measured by open field, light/dark transition task, and prepulse inhibition tests. Moreover, gp120 transgenic mice have an increased number of spines in the amygdala, as well as higher levels of brain-derived neurotrophic factor and tissue plasminogen activator when compared to age-matched wild type. Our data support the hypothesis that HIV, through gp120, may cause structural changes in the amygdala that lead to maladaptive responses to anxiety.
authors: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Alessia
authors: A
authors: Bachis
authors: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Patrick
authors: P
authors: Forcelli
authors: Department of Pathology, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors: Eliezer
authors: E
authors: Masliah
authors: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors: Lee
authors: L
authors: Campbell
authors: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: moccheti@georgetown.edu.
authors: Italo
authors: I
authors: Mocchetti
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis* / Q000235:genetics*; D015658:HIV Infections / Q000378:metabolism* / Q000523:psychology* / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D065808:Prepulse Inhibition
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015699:HIV Envelope Protein gp120
keywords: BDNF; Gp120 transgenic mice; IL-1β; Light–dark transition; Open field; Prepulse inhibition; TNFα; tPA