PMID- 12890780 OWN - NLM STAT- MEDLINE DCOM- 20030903 LR - 20220309 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 17 DP - 2003 Jul 30 TI - Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. PG - 6856-65 AB - Brain-derived neurotrophic factor (BDNF) is thought to be involved in neuronal survival, migration, morphological and biochemical differentiation, and modulation of synaptic function in the CNS. In the rodent cortex, postnatal BDNF expression is initially low but subsequently increases to reach maximal levels around weaning. Thus, BDNF expression peaks at a time when both structural and functional maturation of cortical circuitry occurs. Although the function of BDNF has been probed using many approaches, its requirements during this phase of life have not previously been examined genetically. To test the in vivo requirements for BDNF during this important phase of development we generated early-onset forebrain-specific BDNF mutant mice. Although these mice undergo forebrain-restricted deletion of BDNF by Cre-mediated recombination during embryogenesis, they are healthy, and we did not detect the loss of specific cortical excitatory or inhibitory neurons. However, the neocortex of 5-week-old mice was thinner, attributable at least partly to neuronal shrinkage. Importantly, although visual cortical layer 2/3 neurons in the mutants initially developed normal dendrite structure, dendritic retraction became apparent by 3 weeks of age. Thus, our observations suggest that cortically expressed BDNF functions to support the maintenance of cortical neuron size and dendrite structure rather than the initial development of these features. This is consistent with a role for BDNF in stabilizing the "survival" of circuitry during the phase of activity-dependent reorganization of cortical connectivity. FAU - Gorski, Jessica A AU - Gorski JA AD - Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA. FAU - Zeiler, Steven R AU - Zeiler SR FAU - Tamowski, Susan AU - Tamowski S FAU - Jones, Kevin R AU - Jones KR LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - G6D6147J22 (biocytin) RN - K3Z4F929H6 (Lysine) SB - IM MH - Age Factors MH - Animals MH - Behavior, Animal MH - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/*physiology MH - Cell Count MH - Cell Size MH - Cell Survival/genetics MH - Cerebral Cortex/*metabolism/pathology MH - Dendrites/*metabolism/pathology MH - Female MH - Gene Expression Regulation, Developmental MH - Gene Targeting/methods MH - Lysine/*analogs & derivatives MH - Male MH - Mice MH - Mice, Mutant Strains MH - Neurodegenerative Diseases/genetics/pathology MH - Neurons/metabolism/pathology/ultrastructure MH - Organ Specificity MH - Prosencephalon/metabolism/pathology MH - Pyramidal Cells/pathology/ultrastructure PMC - PMC6740724 EDAT- 2003/08/02 05:00 MHDA- 2003/09/04 05:00 PMCR- 2004/01/30 CRDT- 2003/08/02 05:00 PHST- 2003/08/02 05:00 [pubmed] PHST- 2003/09/04 05:00 [medline] PHST- 2003/08/02 05:00 [entrez] PHST- 2004/01/30 00:00 [pmc-release] AID - 23/17/6856 [pii] AID - 10.1523/JNEUROSCI.23-17-06856.2003 [doi] PST - ppublish SO - J Neurosci. 2003 Jul 30;23(17):6856-65. doi: 10.1523/JNEUROSCI.23-17-06856.2003.