PMID- 22776425 OWN - NLM STAT- MEDLINE DCOM- 20121113 LR - 20171116 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 237 IP - 2 DP - 2012 Oct TI - Age-dependent decline of motor neocortex but not hippocampal performance in heterozygous BDNF mice correlates with a decrease of cortical PSD-95 but an increase of hippocampal TrkB levels. PG - 335-45 LID - S0014-4886(12)00275-0 [pii] LID - 10.1016/j.expneurol.2012.06.033 [doi] AB - Brain-derived neurotrophic factor (BDNF) is a key player in learning and memory processes. However, little is known about brain area-specific functions of this neurotrophin. Here we investigated whether BDNF could differently affect motor neocortical and hippocampal-related cognitive and plastic morphologic changes in young (12-week-old) and middle-aged (30-week-old) BDNF heterozygous (BDNF(+)/(-)) and wild type (wt) mice. We found that at 30 weeks of age, BDNF(+)/(-) mice showed impaired performance in accelerating rotarod and grasping tests while preserved spatial learning in a T-maze and recognition memory in an object recognition task compared with wt mice suggesting a specific neocortical dysfunction. Accordingly, a significant reduction of synaptic markers (PSD-95 and GluR1) and corresponding puncta was observed in motor neocortex but not in hippocampus of BDNF(+)/(-) mice. Interestingly, 30-week-old BDNF(+)/(-) mice displayed increased TrkB levels in the hippocampus but not in the motor neocortex, which suggests specific hippocampal compensatory mechanisms as a consequence of BDNF decrease. In conclusion, our data indicates that BDNF could differentially regulate the neuronal micro-structures and cognition in a region-specific and in an age-dependent manner. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Carreton, Olga AU - Carreton O AD - Departament de Biologia Cellular, Immunologia i Neurociencies, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain. FAU - Giralt, Albert AU - Giralt A FAU - Torres-Peraza, Jesus F AU - Torres-Peraza JF FAU - Brito, Veronica AU - Brito V FAU - Lucas, Jose J AU - Lucas JJ FAU - Gines, Silvia AU - Gines S FAU - Canals, Josep M AU - Canals JM FAU - Alberch, Jordi AU - Alberch J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120706 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, mouse) RN - 0 (Membrane Proteins) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.4.8 (Guanylate Kinases) SB - IM MH - Aging/*physiology MH - Animals MH - Blotting, Western MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Dendritic Spines/metabolism MH - Disks Large Homolog 4 Protein MH - Enzyme-Linked Immunosorbent Assay MH - Guanylate Kinases/*biosynthesis MH - Heterozygote MH - Learning/physiology MH - Membrane Proteins/*biosynthesis MH - Memory/physiology MH - Mice MH - Microscopy, Confocal MH - Neuronal Plasticity/physiology MH - Receptor, trkB/*biosynthesis EDAT- 2012/07/11 06:00 MHDA- 2012/11/14 06:00 CRDT- 2012/07/11 06:00 PHST- 2012/05/30 00:00 [received] PHST- 2012/06/25 00:00 [revised] PHST- 2012/06/28 00:00 [accepted] PHST- 2012/07/11 06:00 [entrez] PHST- 2012/07/11 06:00 [pubmed] PHST- 2012/11/14 06:00 [medline] AID - S0014-4886(12)00275-0 [pii] AID - 10.1016/j.expneurol.2012.06.033 [doi] PST - ppublish SO - Exp Neurol. 2012 Oct;237(2):335-45. doi: 10.1016/j.expneurol.2012.06.033. Epub 2012 Jul 6.