title: Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats.
abstract: BACKGROUND
  Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins.
  
  
  METHODS
  We measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats.
  
  
  RESULTS
  Compared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1β and tumor necrosis factor α, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-κBp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged.
  
  
  CONCLUSIONS
  HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, Bethesda, MD 20892, USA. jrao@mail.nih.gov
authors.forename: Jagadeesh Sridhara
authors.initials: JS
authors.lastname: Rao
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Matthew
authors.initials: M
authors.lastname: Kellom
authors.forename: Dede
authors.initials: D
authors.lastname: Greenstein
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Andrew David
authors.initials: AD
authors.lastname: Kraft
authors.forename: Gaylia Jean
authors.initials: GJ
authors.lastname: Harry
authors.forename: Stanley Isaac
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Mireille
authors.initials: M
authors.lastname: Basselin
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000737:chemistry*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase