Somatic gene transfer of cAMP response element-binding protein attenuates memory impairment in aging rats

Proceedings of the National Academy of Sciences of the United States of America
Alexandre MouravlevMatthew J During

Abstract

cAMP response element-binding protein (CREB) is important for the formation and facilitation of long-term memory in diverse models. However, to our knowledge, involvement of CREB in age-associated memory impairment has not been reported. Here, we use a recombinant adeno-associated virus vector to obtain stable transgenic expression of CREB as well as the inducible cAMP early repressor (ICER) in the hippocampus of adult rats. In a longitudinal study, we show that somatic gene transfer of both CREB and ICER does not alter long-term memory in young (3-month-old) rats. However, at 15 months of age, the same CREB-transduced rats show significantly better long-term memory in spatial-navigation and passive-avoidance tasks compared with their equally aged control littermates, and a threshold effect is evident. In contrast, the aged ICER-transduced rats demonstrate significantly reduced memory in comparison with the same control group. Hippocampal CREB gene transfer prevented the aging-related decrease in long-term memory found in the control rats. These data suggest that elevation of CREB protein levels in a subset of hippocampal neurons as achieved by somatic cell gene transfer might compensate for general deficits in molecular mechan...Continue Reading

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Citations

May 13, 2009·Molecular Neurobiology·Gilyana Borlikova, Shogo Endo
Sep 29, 2011·Molecular Neurobiology·Angel Barco, Hélène Marie
Aug 23, 2011·Journal of Biosciences·Wing-Fu Lai
Jul 30, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Patricia A LawlorMatthew J During
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Dec 4, 2013·Antioxidants & Redox Signaling·Dong-Hee ChoiJongmin Lee
Oct 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Caitlin S LatimerNada M Porter
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Sep 21, 2010·Experimental Gerontology·Michael G Garelick, Brian K Kennedy
May 4, 2010·Physiology & Behavior·Xiang-Dong Xiong, Gui-Hai Chen
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Dec 16, 2006·Brain Research·Alexandre MouravlevMatthew J During
Oct 20, 2006·Experimental Gerontology·Andrzej Bartke
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Feb 21, 2007·Expert Opinion on Biological Therapy·Deborah A Ryan, Howard J Federoff
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