Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats
Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats
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DOI：
10.1016/j.bbi.2005.04.005
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发表时间：
2006-01-01
影响因子：
15.1
通讯作者：
Fang, JD
中科院分区：
文献类型：
--
作者：
Guan, ZW;Fang, JD
内毒素是革兰氏阴性菌的细胞壁成分，可诱导神经元死亡，减少神经发生，损害突触可塑性和记忆，但其作用机制尚不清楚。我们假设大脑中的神经营养素水平受到内毒素的影响。为了验证这一假说，我们测定了内毒素对大鼠腹腔注射生理盐水或内毒素(0.1、0.3或1.0 mg/kg)后脑内脑源性神经营养因子(BDNF)、神经生长因子(NGF)和NT-3水平的影响。脂多糖显著降低海马区(-20%)、额叶皮质(-19%)、顶叶皮质(-63%)、颞叶皮质(-29%)和枕叶皮质(-41%)的BDNF。脂多糖还显著降低了海马区和不同皮质区(枕叶皮质除外)的NGF水平，降幅为10%-20%。最后，内毒素使额叶皮质中的NT-3减少了15-25%。这些观察表明，由神经营养素介导的脑内神经保护作用受到内毒素诱导的全身免疫激活的损害。(C)2005 Elsevier Inc.保留所有权利。
Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, induces neuronal death, decreases neurogenesis, and impairs synaptic plasticity and memory, but the mechanisms for these effects are not well understood. We hypothesize that neurotrophin levels in the brain are influenced by LPS. To test this hypothesis, we determined effects of LPS on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and NT-3 levels in the brain after intraperitoneal injection of saline or LPS (0.1, 0.3 or 1.0 mg/kg) in rats. LPS significantly decreased BDNF in the hippocampus (-20%), frontal cortex (-19%), parictal cortex (-63%), temporal cortex (-29%), and occipital cortex (-41%). LPS also significantly decreased NGF levels by 10-20% in the hippocampus and different cortical regions, except in the occipital cortex. Finally, LPS decreased NT-3 by 15-25% in the frontal cortex. These observations indicate that the neuroprotection mediated by neurotrophins in the brain are compromised by systemic immune activation induced by LPS. (c) 2005 Elsevier Inc. All rights reserved.