Brain regional angiogenic potential at the neurovascular unit during normal aging

Neurobiol Aging. 2012 May;33(5):1004.e1-16. doi: 10.1016/j.neurobiolaging.2011.09.022. Epub 2011 Oct 21.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Cerebral Arteries / growth & development*
  • Cerebral Arteries / physiology
  • Cerebrovascular Circulation / physiology*
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / physiopathology
  • Cerebrovascular Disorders / therapy
  • Disease Models, Animal
  • Exercise Therapy / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / physiology*
  • Physical Conditioning, Animal / methods*