title: Influence of viral vector-mediated delivery of superoxide dismutase and catalase to the hippocampus on spatial learning and memory during aging.
abstract: OBJECTIVE
  Studies employing transgenic mice indicate that overexpression of superoxide dismutase 1 (SOD1) improves memory during aging. It is unclear whether the improvement is due to a lifetime of overexpression, decreasing the accumulation of oxidized molecules, or if increasing antioxidant enzymes in older animals could reduce oxidative damage and improve cognitive function. We used adeno-associated virus to deliver antioxidant enzymes (SOD1, SOD2, catalase [CAT], and SOD1+CAT) to the hippocampus of young (4 months) and aged (19 months) F344/BN F1 male rats and examined memory-related behavioral performance 1 month and 4 months postinjection.
  
  
  RESULTS
  Overexpression of antioxidant enzymes reduced oxidative damage; however, memory function was not related to the level of oxidative damage. Increased expression of SOD1, initiated in advanced age, impaired learning. Increased expression of SOD1+CAT provided protection from impairments associated with overexpression of SOD1 alone and appears to guard against cognitive impairments in advanced age.
  
  
  METHODS
  Viral vector gene delivery provides a novel approach to test the hypothesis that increased expression of antioxidant enzymes, specifically in hippocampal neurons, will provide protection from age-related cognitive decline. Further, expression of multiple vectors permits more detailed investigation of mechanistic pathways.
  
  
  CONCLUSIONS
  Oxidative stress is a likely component of aging; however, it is unclear whether increased production of reactive oxygen species or the accumulation of oxidative damage is the primary cause of functional decline. The results provide support for the idea that altered redox-sensitive signaling rather than the accumulation of damage may be of greater significance in the emergence of age-related learning and memory deficits.
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida , Gainesville, Florida 32610-0244, USA.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Lee
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Asha
authors.initials: A
authors.lastname: Rani
authors.forename: Jose
authors.initials: J
authors.lastname: Herrera
authors.forename: Jinze
authors.initials: J
authors.lastname: Xu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Someya
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Foster
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D011916:Rats, Inbred F344; D013037:Spatial Behavior; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D002374:Catalase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat