title: Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory.
abstract: Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of people with HIV associated dementia suggesting that astrocytic Nef may contribute to HIV associated cognitive impairment even when viral replication is suppressed. To test whether astrocytic expression of Nef is sufficient to induce cognitive deficits, we examined the effect of implanting primary rat astrocytes expressing Nef into the hippocampus on spatial and recognition memory. Rats implanted unilaterally with astrocytes expressing Nef showed impaired novel location and novel object recognition in comparison with controls implanted with astrocytes expressing green fluorescent protein (GFP). This impairment was correlated with an increase in chemokine ligand 2 (CCL2) expression and the infiltration of peripheral macrophages into the hippocampus at the site of injection. Furthermore, the Nef exposed rats exhibited a bilateral loss of CA3 neurons. These results suggest that Nef protein expressed by the implanted astrocytes activates the immune system leading to neuronal damage and spatial and recognition memory deficits. Therefore, the continued expression of Nef by astrocytes in the absence of viral replication has the potential to contribute to HIV associated cognitive impairment.
authors.affiliation: Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR, USA.
authors.forename: Gladys
authors.initials: G
authors.lastname: Chompre
authors.affiliation: Department of Physiology & Pharmacology, Ponce School of Medicine and Health Sciences, Ponce, PR, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cruz
authors.affiliation: Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR, USA.
authors.forename: Lucianette
authors.initials: L
authors.lastname: Maldonado
authors.affiliation: Department of Microbiology, Ponce School of Medicine and Health Sciences, Ponce, PR, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rivera-Amill
authors.affiliation: Department of Physiology & Pharmacology, Ponce School of Medicine and Health Sciences, Ponce, PR, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Porter
authors.affiliation: Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR, USA. Electronic address: rnoel@psm.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Noel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000503:physiopathology; D001253:Astrocytes / Q000378:metabolism*; D016380:Brain Tissue Transplantation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology*; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D049452:Green Fluorescent Proteins