caa a22 4500 606203516 CHVBK 20210128100958.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00429-013-0676-6 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0676-6 Effects of chronic HIV-1 Tat exposure in the CNS: heightened vulnerability of males versus females to changes in cell numbers, synaptic integrity, and behavior [Elektronische Daten] [Yun Hahn, Elizabeth Podhaizer, Sean Farris, Michael Miles, Kurt Hauser, Pamela Knapp] HIV-associated damage to the central nervous system results in cognitive and motor deficits. Anti-retroviral therapies reduce the severity of symptoms, yet the proportion of patients affected has remained the same or increased. Although approximately half of HIV-infected patients worldwide are women, the question of whether biological sex influences outcomes of HIV infection has received little attention. We explored this question for both behavioral and cellular/morphologic endpoints, using a transgenic mouse that inducibly expresses HIV-1 Tat in the brain. After 3months of HIV-1 Tat exposure, both sexes showed similar reduced open field ambulation. Male Tat+ mice also showed reduced forelimb grip strength and enhanced anxiety in a light-dark box assay. Tat+ males did not improve over 12weeks of repeated rotarod testing, indicating a motor memory deficit. Male mice also had more cellular deficits in the striatum. Neither sex showed a change in volume or total neuron numbers. Both had equally reduced oligodendroglial populations and equivalent microglial increases. However, astrogliosis and microglial nitrosative stress were higher in males. Dendrites on medium spiny neurons in male Tat+ mice had fewer spines, and levels of excitatory and inhibitory pre- and post-synaptic proteins were disrupted. Our results predict sex as a determinant of HIV effects in brain. Increased behavioral deficits in males correlated with glial activation and synaptic damage, both of which are implicated in cognitive/motor impairments in patients. Tat produced by residually infected cells despite antiretroviral therapy may be an important determinant of the synaptodendritic instability and behavioral deficits accompanying chronic infection. The Author(s), 2013 Striatum nationallicence NeuroAIDS nationallicence Tat nationallicence HIV-1 nationallicence Sex nationallicence Behavior nationallicence Hahn Yun Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, PO Box 980709, 23298-0709, Richmond, VA, USA aut Podhaizer Elizabeth Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut Farris Sean Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut Miles Michael Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut Hauser Kurt Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut Knapp Pamela Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, PO Box 980709, 23298-0709, Richmond, VA, USA aut Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 605-623 1863-2653 220:2<605 2015 220 429 https://doi.org/10.1007/s00429-013-0676-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0676-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hahn Yun Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, PO Box 980709, 23298-0709, Richmond, VA, USA aut NATIONALLICENCE 700 1- Podhaizer Elizabeth Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut NATIONALLICENCE 700 1- Farris Sean Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut NATIONALLICENCE 700 1- Miles Michael Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut NATIONALLICENCE 700 1- Hauser Kurt Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, 23298-0613, Richmond, VA, USA aut NATIONALLICENCE 700 1- Knapp Pamela Department of Anatomy and Neurobiology, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, PO Box 980709, 23298-0709, Richmond, VA, USA aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 605-623 1863-2653 220:2<605 2015 220 429