title: Attenuation of brain response to vascular endothelial growth factor-mediated angiogenesis and neurogenesis in aged mice.
abstract: OBJECTIVE
  Alterations of neuroangiogenic response play important roles in the development of aging-related neurodisorders and affect gene-based therapies. We tested brain response to vascular endothelial growth factor (VEGF) in aged mice.
  
  
  METHODS
  Adeno-associated viral vector (AAV)-VEGF, an adeno-associated viral vector expressing VEGF, was injected into the brain of 3-, 12-, and 24-month-old mice. AAV-LacZ-injected mice were used as controls (n=6). Before euthanasia at 6 weeks after vector injection, the mice were intraperitoneally injected with 5-bromodeoxyuridine for 3 consecutive days. The vascular density and the number of neuroprogenitors were analyzed.
  
  
  RESULTS
  Injection of AAV-VEGF increased the vascular density in the brain of 3-, 12-, and 24-month-old mice by 22%+/-7% (AAV-VEGF: 320+/-15 per 10x field versus AAV-LacZ: 263+/-8, P<0.05), 20%+/-8 (AAV-VEGF: 300+/-9 versus AAV-LacZ: 250+/-11, P<0.05), and 7%+/-16% (AAV-VEGF: 257+/-27 versus AAV-LacZ: 236+/-13, P=0.283), respectively. There were more VEGF receptor-positive neuroprogenitors in the subventricular zone of AAV-VEGF-injected 3- (22+/-2) and 12-month-old mice (21+/-5) than that of 24-month-old mice (7+/-1). More 5-bromodeoxyuridine-positive endothelial cells and neuroprogenitors were detected around the injection site and subventricular zone of 3- (13+/-4) and 12-month-old mice (14+/-5) than that of 24-month-old mice (1+/-1). VEGF receptor 2 was upregulated in AAV-VEGF-injected brains of 3- and 12-month-old mice, but not in 24-month-old mice.
  
  
  CONCLUSIONS
  The angiogenic and neurogenic response to VEGF stimulation is attenuated in the aged mouse brain, which may be due to reduced VEGF receptor activity.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, Center for Cerebrovascular Research, San Francisco, Calif 94110, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Fanxia
authors.initials: F
authors.lastname: Shen
authors.forename: Rodney Allanigue
authors.initials: RA
authors.lastname: Gabriel
authors.forename: David
authors.initials: D
authors.lastname: Law
authors.forename: Ethan Yibo
authors.initials: EY
authors.lastname: Yang
authors.forename: Ethan
authors.initials: E
authors.lastname: Yang
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: Hua
authors.initials: H
authors.lastname: Su
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A