title: 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.
abstract: 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.
authors: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Olga
authors: O
authors: Carretón
authors: Albert
authors: A
authors: Giralt
authors: Jesús F
authors: JF
authors: Torres-Peraza
authors: Verónica
authors: V
authors: Brito
authors: José J
authors: JJ
authors: Lucas
authors: Sílvia
authors: S
authors: Ginés
authors: Josep M
authors: JM
authors: Canals
authors: Jordi
authors: J
authors: Alberch
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004797:Enzyme-Linked Immunosorbent Assay; D051528:Guanylate Kinases / Q000096:biosynthesis*; D006579:Heterozygote; D007858:Learning / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis*; D008568:Memory / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000502:physiology; D020813:Receptor, trkB / Q000096:biosynthesis*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D020813:Receptor, trkB; D051528:Guanylate Kinases