title: Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior.
abstract: Brain-derived neurotrophic factor (BDNF) plays important roles in the development, maintenance, and plasticity of the mammalian forebrain. These functions include regulation of neuronal maturation and survival, axonal and dendritic arborization, synaptic efficacy, and modulation of complex behaviors including depression and spatial learning. Although analysis of mutant mice has helped establish essential developmental functions for BDNF, its requirement in the adult is less well documented. We have studied late-onset forebrain-specific BDNF knockout (CaMK-BDNF(KO)) mice, in which BDNF is lost primarily from the cortex and hippocampus in early adulthood, well after BDNF expression has begun in these structures. We found that although CaMK-BDNF(KO) mice grew at a normal rate and can survive more than a year, they had smaller brains than wild-type siblings. The CaMK-BDNF(KO) mice had generally normal behavior in tests for ataxia and anxiety, but displayed reduced spatial learning ability in the Morris water task and increased depression in the Porsolt swim test. These behavioral deficits were very similar to those we previously described in an early-onset forebrain-specific BDNF knockout. To identify an anatomical correlate of the abnormal behavior, we quantified dendritic spines in cortical neurons. The spine density of CaMK-BDNF(KO) mice was normal at P35, but by P84, there was a 30% reduction in spine density. The strong similarities we find between early- and late-onset BDNF knockouts suggest that BDNF signaling is required continuously in the CNS for the maintenance of some forebrain circuitry also affected by developmental BDNF depletion.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, 347 UCB, University of Colorado, Boulder, CO 80309, USA. vigers@colorado.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Vigers
authors.forename: D S
authors.initials: DS
authors.lastname: Amin
authors.forename: T
authors.initials: T
authors.lastname: Talley-Farnham
authors.forename: J A
authors.initials: JA
authors.lastname: Gorski
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.forename: K R
authors.initials: KR
authors.lastname: Jones
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D019208:Brain-Derived Neurotrophic Factor