Deletion of the lifespan determinant p66Shc improves performance in a spatial memory task, decreases levels of oxidative stress markers in the hippocampus and increases levels of the neurotrophin BDNF in adult mice

A. Berry, A. Greco, M. Giorgio, P. G. Pelicci, R. de Kloet, E. Alleva, L. Minghetti, F. Cirulli

Research output: Contribution to journalArticle

Abstract

Deletion of the p66Shc gene in mice results in reduced levels of oxidative stress and longer lifespan. Reactive oxygen species (ROS) can lead to tissue damage, particularly in the brain. In this study we extended previous findings on the behavioral phenotype of the p66Shc-/- mice. Cognitive performance of adult and old p66Shc-/- and p66Shc+/+ mice was tested in a Morris water maze (MWM) task while general reactivity and pain sensitivity were assayed at adulthood, respectively, in an open field and by means of a tail flick test. Levels of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in several aspects of synaptic plasticity, emotionality and pain sensitivity, were assessed in selected brain areas. P66Shc-/- adult subjects, compared to WT, overall showed a better performance in the MWM, lower emotionality and a higher pain threshold, in addition to increased basal levels of BDNF in the hippocampus, as well as decreased levels of oxidative stress markers in the same brain area. Although all aged subjects failed to learn the cognitive task, aged p66Shc-/- mice were characterized by a better physical performance. These results suggest an interaction between the p66Shc gene and specific signaling pathways involved in behavioral adaptation to stress and aging.

Original languageEnglish
Pages (from-to)200-208
Number of pages9
JournalExperimental Gerontology
Volume43
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Aging
  • Anxiety
  • BDNF
  • Mice
  • Morris water maze
  • Neurodegeneration
  • Open field
  • Oxidative stress
  • p66
  • Pain sensitivity

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

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