Deletion of the lifespan determinant p66(Shc) 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.
Deletion of the p66(Shc) 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 p66(Shc-/-) mice. Cognitive performance of adult and old p66(Shc-/-) and p66(Shc+/+) 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. P66(Shc-/-) 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 p66(Shc-/-) mice were characterized by a better physical performance. These results suggest an interaction between the p66(Shc) gene and specific signaling pathways involved in behavioral adaptation to stress and aging.
Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
A
A
Berry
A
A
Greco
M
M
Giorgio
P G
PG
Pelicci
R
R
de Kloet
E
E
Alleva
L
L
Minghetti
F
F
Cirulli
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000502:physiology; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010146:Pain / Q000235:genetics / Q000503:physiopathology; D017288:Pain Threshold; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1