title: GSK-3β overexpression causes reversible alterations on postsynaptic densities and dendritic morphology of hippocampal granule neurons in vivo.
abstract: Adult hippocampal neurogenesis (AHN) is crucial for the maintenance of hippocampal function. Several neurodegenerative diseases such as Alzheimer's disease (AD) are accompanied by memory deficits that could be related to alterations in AHN. Here, we took advantage of a conditional mouse model to study the involvement of glycogen synthase kinase-3β (GSK-3β) overexpression (OE) in AHN. By injecting GFP- and PSD95-GFP-expressing retroviruses, we have determined that hippocampal GSK-3β-OE causes dramatic alterations in both dendritic tree morphology and post-synaptic densities in newborn neurons. Alterations in previously damaged neurons were reverted by switching off the transgenic system and also by using a physiological approach (environmental enrichment) to increase hippocampal plasticity. Furthermore, comparative morphometric analysis of granule neurons from patients with AD and from GSK-3β overexpressing mice revealed shared morphological alterations. Taken together, these data indicate that GSK-3β is crucial for hippocampal function, thereby supporting this kinase as a relevant target for the treatment of AD.
authors: Department of Molecular Neurobiology, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
authors: M
authors: M
authors: Llorens-Martín
authors: A
authors: A
authors: Fuster-Matanzo
authors: C M
authors: CM
authors: Teixeira
authors: J
authors: J
authors: Jurado-Arjona
authors: F
authors: F
authors: Ulloa
authors: J
authors: J
authors: Defelipe
authors: A
authors: A
authors: Rábano
authors: F
authors: F
authors: Hernández
authors: E
authors: E
authors: Soriano
authors: J
authors: J
authors: Avila
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D003712:Dendrites / Q000648:ultrastructure*; D004777:Environment; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis* / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000033:anatomy & histology* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D057907:Post-Synaptic Density / Q000648:ultrastructure*; D015854:Up-Regulation
chemical_list: C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3