Blood-Brain Barrier Laboratory, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Neurobiol Aging. 2012 May;33(5):1004.e1-16. doi: 10.1016/j.neurobiolaging.2011.09.022. Epub 2011 Oct 21.
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 versus aged mice by laser capture microdissection coupled to quantitative real-time polymerase chain reaction (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.
鉴于大脑具有强烈的区域专业化特征，脑血管生成在正常衰老过程中可能会发生区域性改变。为了验证这一假设，通过激光捕获显微切割和实时定量聚合酶链反应 (PCR)，对年轻和老年小鼠不同脑区的神经血管单元 (NVU) 中广泛的血管生成相关基因表达进行了检测。还进行了补充的定量毛细血管密度/分支研究。还检测了体育锻炼的效果，以确定是否可以逆转与年龄相关的趋势。此外，还探测了基因对缺氧的反应，以突出与年龄相关的适应这种血管生成压力的弱点。衰老以区域依赖的方式影响 NVU 中血管生成相关基因的静息表达。体育锻炼逆转了其中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，缺氧揭示了老年大脑中较弱的血管生成反应。这些结果表明，在正常衰老过程中，大脑的血管生成能力发生了异质性变化，并暗示了物理锻炼在 NVU 水平上具有治疗益处。
