Molecular manipulations of extracellular superoxide dismutase: functional importance for learning.

Published

Journal Article

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O2.-), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impared by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. No systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (NG-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular O2.- may be more vital than merely reduction of brain extracellular O2.- in maintaining adequate learning function.

Full Text

Duke Authors

Cited Authors

  • Levin, ED; Brady, TC; Hochrein, EC; Oury, TD; Jonsson, LM; Marklund, SL; Crapo, JD

Published Date

  • September 1998

Published In

Volume / Issue

  • 28 / 5

Start / End Page

  • 381 - 390

PubMed ID

  • 9926619

Pubmed Central ID

  • 9926619

International Standard Serial Number (ISSN)

  • 0001-8244

Language

  • eng

Conference Location

  • United States