title: Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse.
abstract: HIV-Tat protein has been implicated in the pathogenesis of HIV-1 neurological complications (i.e., neuroAIDS), but direct demonstrations of the effects of Tat on behavior are limited. GT-tg mice with a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein were used to test the hypothesis that the activity of Tat in brain is sufficient to impair learning and memory processes. Western blot analysis of GT-tg mouse brains demonstrated an increase in Tat antibody labeling that seemed to be dependent on the dose and duration of Dox pretreatment. Dox-treated GT-tg mice tested in the Barnes maze demonstrated longer latencies to find an escape hole and displayed deficits in probe trial performance versus uninduced GT-tg littermates, suggesting Tat-induced impairments of spatial learning and memory. Reversal learning was also impaired in Tat-induced mice. Tat-induced mice additionally demonstrated long-lasting (up to one month) deficiencies in novel object recognition learning and memory performance. Furthermore, novel object recognition impairment was dependent on the dose and duration of Dox exposure, suggesting that Tat exposure progressively mediated deficits. These experiments provide evidence that Tat protein expression is sufficient to mediate cognitive abnormalities seen in HIV-infected individuals. Moreover, the genetically engineered GT-tg mouse may be useful for improving our understanding of the neurological underpinnings of neuroAIDS-related behaviors.
authors.affiliation: Northeastern University, Department of Psychology, 360 Huntington Ave., Boston, MA 02115, USA.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Carey
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Sypek
authors.forename: Harminder D
authors.initials: HD
authors.lastname: Singh
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Kaufman
authors.forename: Jay P
authors.initials: JP
authors.lastname: McLaughlin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors
chemical_list: D015696:Gene Products, tat; D005904:Glial Fibrillary Acidic Protein; D004318:Doxycycline