Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats.
Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats.
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DOI：
10.1186/1742-2094-8-101
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发表时间：
2011-08-16
影响因子：
9.3
通讯作者：
Basselin M
中科院分区：
文献类型：
--
作者：
Rao JS;Kim HW;Kellom M;Greenstein D;Chen M;Kraft AD;Harry GJ;Rapoport SI;Basselin M
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. 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. 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. 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.
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影响因子：
14.9
作者：
Dandekar, DH;Ganesh, KN;Mitra, D
通讯作者：
Mitra, D
影响因子：
15.1
作者：
Fiore, M;Probert, L;Aloe, L
通讯作者：
Aloe, L
DOI：
10.1093/jnen/60.9.893
发表时间：
2001-09-01
影响因子：
3.2
作者：
Blais, V;Rivest, S
通讯作者：
Rivest, S
影响因子：
5.3
作者：
Flora, G;Lee, YW;Toborek, M
通讯作者：
Toborek, M
影响因子：
11.2
作者：
GRIFFIN, DE;WESSELINGH, SL;MCARTHUR, JC
通讯作者：
MCARTHUR, JC