PMID- 22019053 OWN - NLM STAT- MEDLINE DCOM- 20121123 LR - 20240315 IS - 1558-1497 (Electronic) IS - 0197-4580 (Print) IS - 0197-4580 (Linking) VI - 33 IP - 5 DP - 2012 May TI - Brain regional angiogenic potential at the neurovascular unit during normal aging. PG - 1004.e1-16 LID - 10.1016/j.neurobiolaging.2011.09.022 [doi] AB - 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. CI - Copyright A(c) 2012 Elsevier Inc. All rights reserved. FAU - Murugesan, Nivetha AU - Murugesan N AD - Blood-Brain Barrier Laboratory, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA. FAU - Demarest, Tyler G AU - Demarest TG FAU - Madri, Joseph A AU - Madri JA FAU - Pachter, Joel S AU - Pachter JS LA - eng GR - R01 HL051018/HL/NHLBI NIH HHS/United States GR - R21 NS057241/NS/NINDS NIH HHS/United States GR - R01 MH054718/MH/NIMH NIH HHS/United States GR - R01 MH054718-04/MH/NIMH NIH HHS/United States GR - R01-HL51018/HL/NHLBI NIH HHS/United States GR - R21 NS057241-01/NS/NINDS NIH HHS/United States GR - P01-NS00344738/NS/NINDS NIH HHS/United States GR - R21-NS057241/NS/NINDS NIH HHS/United States GR - R0-1-MH54718/MH/NIMH NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20111021 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 SB - IM MH - Aging/*physiology MH - Animals MH - Cerebral Arteries/*growth & development/physiology MH - Cerebrovascular Circulation/*physiology MH - Cerebrovascular Disorders/genetics/physiopathology/therapy MH - Disease Models, Animal MH - Exercise Therapy/*methods MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neovascularization, Physiologic/*physiology MH - Physical Conditioning, Animal/*methods PMC - PMC3266473 MID - NIHMS327980 COIS- Disclosure statement The authors have no actual or potential conflicts of interest. All animal treatments were reviewed and approved by the Institutional Animal Care and Use Committee and were in accordance with guidelines stipulated by the Animal Care and Use Guidelines of the University of Connecticut Health Center and the Yale University Animal Care Committee. EDAT- 2011/10/25 06:00 MHDA- 2012/12/10 06:00 PMCR- 2013/05/01 CRDT- 2011/10/25 06:00 PHST- 2011/05/11 00:00 [received] PHST- 2011/08/18 00:00 [revised] PHST- 2011/09/15 00:00 [accepted] PHST- 2011/10/25 06:00 [entrez] PHST- 2011/10/25 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] PHST- 2013/05/01 00:00 [pmc-release] AID - S0197-4580(11)00374-5 [pii] AID - 10.1016/j.neurobiolaging.2011.09.022 [doi] PST - ppublish SO - Neurobiol Aging. 2012 May;33(5):1004.e1-16. doi: 10.1016/j.neurobiolaging.2011.09.022. Epub 2011 Oct 21.