RESUMO
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-1ß 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.
Assuntos
Ácido Araquidônico/metabolismo , Encefalite/metabolismo , HIV-1/genética , Ratos Transgênicos , Transdução de Sinais/fisiologia , Sinapses/química , Animais , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Ácido Araquidônico/química , Biomarcadores/metabolismo , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Encefalite/patologia , HIV-1/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Endogâmicos F344 , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors. The National Institutes of Health has found that Dr. Jagadeesh S. Rao engaged in research misconduct by falsifying data. Data in Figures 1A, 1E, 3E and 3F were falsified. Dr. Rao was solely responsible for the falsification. None of the other authors are implicated in any way.
Assuntos
Ácido Araquidônico/metabolismo , Citocinas/metabolismo , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Esquizofrenia/complicações , Esquizofrenia/patologia , Adulto , Idoso , Análise de Variância , Citocinas/genética , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Masculino , Microglia/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/síntese química , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Mudanças Depois da Morte , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro , Receptores de N-Metil-D-AspartatoRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of The National Institutes of Health has found that the first author, Dr. Jagadeesh S. Rao engaged in research misconduct by falsifying data in "Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients". Rao JS, Kellom M, Reese EA, Rapoport SI, Kim HW. J. Affect Disord. 136(12):6371. 2012. Data in Figures 2A, 2B, 3A, 3B and 4A were falsified.