期刊
NEUROBIOLOGY OF AGING
卷 33, 期 5, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.09.022
关键词
Brain microvasculature; Cerebral angiogenesis; Normal aging; Laser capture microdissection; Neurovascular unit
资金
- National Institutes of Health [RO-1-MH54718, R21-NS057241]
- National Multiple Sclerosis Society [PP-1215]
- Connecticut Dept. of Public Health [2011-0143]
- American Heart Association [0815733D]
- [PO1-NS00344738]
- [RO1-HL51018]
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. (C) 2012 Elsevier Inc. All rights reserved.
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