title: Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice.
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.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy. francesco.papaleo@iit.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Papaleo
authors.forename: Jill L
authors.initials: JL
authors.lastname: Silverman
authors.forename: Jordan
authors.initials: J
authors.lastname: Aney
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Tian
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Barkan
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Chadman
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Crawley
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003623:Dark Adaptation / Q000235:genetics; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000523:psychology; D005260:Female; D019417:Hindlimb Suspension / Q000379:methods; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010147:Pain Measurement; D045442:Rotarod Performance Test; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D012919:Social Behavior; D013550:Swimming / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor