Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain

Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain
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DOI:
10.1016/j.bbi.2009.09.012
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发表时间:
2010-03-01
影响因子:
15.1
通讯作者:
Bilbo, Staci D.
Bilbo, Staci D.
中科院分区:
医学1区
文献类型:
--
作者:
Bland, Sondra T.;Beckley, Jacob T.;Bilbo, Staci D.

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大鼠出生后第4天(P)全身感染大肠埃希氏菌导致成年期脑细胞因子反应和行为变化的显着改变,但仅响应于随后的脂多糖[LPS]免疫攻击。这些变化的基础可能是神经胶质细胞功能的长期变化。我们评估了新生儿感染后海马、顶叶皮质(PAR)和前额叶皮质(PFC)的胶质细胞和神经细胞发生,以及成年后对LPS的反应。E.与对照组相比,大肠杆菌增加了海马和PAR内新生小胶质细胞的数量。E.大肠杆菌处理的幼崽,伴随着总增殖的减少。P33时,E.与对照组相比,在成年期,齿状回(DG)内的基础神经发生没有组间差异;然而,在响应LPS,有一个早期感染大鼠的神经发生减少,但在控制相同的挑战增加。也有显着更多的小胶质细胞在成年DG的早期感染的大鼠,虽然小胶质细胞增殖反应LPS在对照组增加。综上所述,我们提供的证据表明,全身感染E。大肠杆菌在生命早期对大脑发育和随后的成年功能具有重大而持久的影响。这些变化包括神经胶质的显著改变,以及对认知重要的大脑区域的神经发生的影响。(C)2009 Elsevier Inc. All rights reserved.
Systemic infection with Eschetichia coli on postnatal day (P) 4 in rats results in significantly altered brain cytokine responses and behavioral changes in adulthood, but only in response to a subsequent immune challenge with lipopoiysaccharide [LPS]. The basis for these changes may be long-term changes in glial cell function. We assessed glial and neural cell genesis in the hippocampus, parietal cortex (PAR), and prefrontal cortex (PFC), in neonates just after the infection, as well as in adulthood in response to LPS. E. coli increased the number of newborn microglia within the hippocampus and PAR compared to controls. The total number of microglia was also significantly increased in E. coli-treated pups, with a concomitant decrease in total proliferation. On P33, there were large decreases in numbers of cells coexpressing BrdU and NeuN in all brain regions of E. coli rats compared to controls. In adulthood, basal neurogenesis within the dentate gyrus (DG) did not differ between groups; however, in response to LPS, there was a decrease in neurogenesis in early-infected rats, but an increase in controls to the same challenge. There were also significantly more microglia in the adult DG of early-infected rats, although microglial proliferation in response to LPS was increased in controls. Taken together, we have provided evidence that systemic infection with E. coli early in life has significant, enduring consequences for brain development and subsequent adult function. These changes include marked alterations in glia, as well as influences on neurogenesis in brain regions important for cognition. (C) 2009 Elsevier Inc. All rights reserved.