Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice
- Francesco Papaleo1,2,4,6,
- Jill L. Silverman3,4,
- Jordan Aney2,
- Qingjun Tian2,
- Charlotte L. Barkan3,
- Kathryn K. Chadman3,5 and
- Jacqueline N. Crawley3
- 1Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy
- 2Clinical Brain Disorders Branch; Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20812, USA
- 3Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20812, USA
Abstract
BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders.
Footnotes
- Received March 15, 2011.
- Accepted June 10, 2011.
