title: Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET.
abstract: Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era.
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Reid
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rafael
authors.initials: R
authors.lastname: Casas
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Papadakis
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Siva
authors.initials: S
authors.lastname: Muthusamy
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Dianne E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Wael G
authors.initials: WG
authors.lastname: Ibrahim
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Anand
authors.initials: A
authors.lastname: Nair
authors.affiliation: Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Deloris
authors.initials: D
authors.lastname: Koziol
authors.affiliation: Division of Intermural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
mesh_terms: D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal; D019788:Fluorodeoxyglucose F18; D015497:HIV-1 / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D049268:Positron-Emission Tomography; D051381:Rats; D055647:Rats, Transgenic
chemical_list: D019788:Fluorodeoxyglucose F18