title: TrkB in the hippocampus and nucleus accumbens differentially modulates depression-like behavior in mice.
abstract: Brain-derived neurotrophic factor (BDNF) exerts antidepressant-like effects in the hippocampus and pro-depressant effects in the nucleus accumbens (NAc). It is thought that downstream signaling of the BDNF receptor TrkB mediates the effects of BDNF in these brain structures. Here, we evaluate how TrkB regulates affective behavior in the hippocampus and NAc. We overexpressed TrkB by electroporating a non-viral plasmid in the NAc or hippocampus in mice. Depression- and anxiety-like behaviors were evaluated in the sucrose test (anhedonia), the forced swim test (despair) and the elevated zero maze (anxiety). Targeted brain tissue was biochemically analyzed to identify molecular mechanisms responsible for the observed behavior. Overexpressing TrkB in the NAc increased the number of young neuronal cells and decreased despair and basal corticosterone levels. TrkB overexpression in the hippocampus increased astrocyte production and activation of the transcription factor CREB, yet without altering affective behavior. Our data suggest antidepressant effects of BDNF-TrkB in the NAc, which could not be explained by activation of the transcription factors CREB or β-catenin. The effects TrkB has on depression-related behavior in different brain regions appear to critically depend on the targeted cell type.
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Jochen
authors: J
authors: De Vry
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Tim
authors: T
authors: Vanmierlo
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Pilar
authors: P
authors: Martínez-Martínez
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Mario
authors: M
authors: Losen
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands; Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Yasin
authors: Y
authors: Temel
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Janneke
authors: J
authors: Boere
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Gunter
authors: G
authors: Kenis
authors: Neurosciences, Janssen R&D, Beerse, Belgium.
authors: Thomas
authors: T
authors: Steckler
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Harry W M
authors: HWM
authors: Steinbusch
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors: Marc De
authors: M
authors: Baets
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
authors: Jos
authors: J
authors: Prickaerts
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*
chemical_list: D020813:Receptor, trkB; D003345:Corticosterone
keywords: Depression; Electroporation; Hippocampus; Nucleus Accumbens; TrkB