Brain regional angiogenic potential at the neurovascular unit during normal aging.

Brain regional angiogenic potential at the neurovascular unit during normal aging.
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DOI:
10.1016/j.neurobiolaging.2011.09.022
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发表时间:
2012-05
影响因子:
4.2
通讯作者:
Pachter JS
Pachter JS
中科院分区:
医学2区
文献类型:
--
作者:
Murugesan N;Demarest TG;Madri JA;Pachter JS

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鉴于大脑的强区域特化,脑血管生成可能在正常衰老期间被区域性地修改。为了验证这一假设,通过激光捕获显微切割结合定量实时PCR,在年轻小鼠与老年小鼠的离散脑区域中的神经血管单位(NVU)处测定了广泛的血管生成相关基因的表达。还进行了补充定量毛细血管密度/分支研究。体育锻炼的影响也进行了分析,以确定是否可以扭转与年龄有关的趋势。此外,对缺氧的基因反应进行了探索,以突出与年龄相关的适应这种血管生成应激的弱点。衰老以区域依赖性方式影响NVU血管生成相关基因的静息表达。体育锻炼逆转了一些与年龄相关的基因趋势,并以区域依赖的方式积极影响脑毛细血管密度/分支。最后,缺氧显示老年脑血管生成反应较弱。这些结果表明,在正常老化过程中,大脑血管生成能力的异质性变化,并暗示在NVU水平上起作用的体育锻炼的治疗益处。
Given strong regional specialization of the brain, cerebral angiogenesis may be regionally modified during normal aging. To test this hypothesis, expression of a broad cadre of angiogenesis-associated genes was assayed at the neurovascular unit (NVU) in discrete brain regions of young vs. aged mice by laser capture microdissection coupled to quantitative real-time PCR. Complementary quantitative capillary density/branching studies were performed as well. Effects of physical exercise were also assayed to determine if age-related trends could be reversed. Additionally, gene response to hypoxia was probed to highlight age-associated weaknesses in adapting to this angiogenic stress. Aging impacted resting expression of angiogenesis-associated genes at the NVU in a region-dependent manner. Physical exercise reversed some of these age-associated gene trends, as well as positively influenced cerebral capillary density/branching in a region-dependent way. Lastly, hypoxia revealed a weaker angiogenic response in aged brain. These results suggest heterogeneous changes in angiogenic capacity of the brain during normal aging, and imply a therapeutic benefit of physical exercise that acts at the level of the NVU.
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