PMID- 18065182 OWN - NLM STAT- MEDLINE DCOM- 20080801 LR - 20161124 IS - 0531-5565 (Print) IS - 0531-5565 (Linking) VI - 43 IP - 3 DP - 2008 Mar TI - 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. PG - 200-8 AB - 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. FAU - Berry, A AU - Berry A AD - Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy. FAU - Greco, A AU - Greco A FAU - Giorgio, M AU - Giorgio M FAU - Pelicci, P G AU - Pelicci PG FAU - de Kloet, R AU - de Kloet R FAU - Alleva, E AU - Alleva E FAU - Minghetti, L AU - Minghetti L FAU - Cirulli, F AU - Cirulli F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071107 PL - England TA - Exp Gerontol JT - Experimental gerontology JID - 0047061 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Shc Signaling Adaptor Proteins) RN - 0 (Shc1 protein, mouse) RN - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1) SB - IM MH - Adaptor Proteins, Signal Transducing/*genetics/physiology MH - Aging/*genetics/physiology MH - Animals MH - Behavior, Animal MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Hippocampus/*metabolism MH - Male MH - Maze Learning/*physiology MH - Mice MH - Mice, Knockout MH - Oxidative Stress/genetics/physiology MH - Pain/genetics/physiopathology MH - Pain Threshold MH - Shc Signaling Adaptor Proteins MH - Signal Transduction/genetics/physiology MH - Spatial Behavior/physiology MH - Src Homology 2 Domain-Containing, Transforming Protein 1 EDAT- 2007/12/11 09:00 MHDA- 2008/08/02 09:00 CRDT- 2007/12/11 09:00 PHST- 2007/09/09 00:00 [received] PHST- 2007/10/26 00:00 [revised] PHST- 2007/10/31 00:00 [accepted] PHST- 2007/12/11 09:00 [pubmed] PHST- 2008/08/02 09:00 [medline] PHST- 2007/12/11 09:00 [entrez] AID - S0531-5565(07)00252-5 [pii] AID - 10.1016/j.exger.2007.10.016 [doi] PST - ppublish SO - Exp Gerontol. 2008 Mar;43(3):200-8. doi: 10.1016/j.exger.2007.10.016. Epub 2007 Nov 7.