title: CDK5 downregulation enhances synaptic plasticity.
abstract: CDK5 is a serine/threonine kinase that is involved in the normal function of the adult brain and plays a role in neurotransmission and synaptic plasticity. However, its over-regulation has been associated with Tau hyperphosphorylation and cognitive deficits. Our previous studies have demonstrated that CDK5 targeting using shRNA-miR provides neuroprotection and prevents cognitive deficits. Dendritic spine morphogenesis and forms of long-term synaptic plasticity-such as long-term potentiation (LTP)-have been proposed as essential processes of neuroplasticity. However, whether CDK5 participates in these processes remains controversial and depends on the experimental model. Using wild-type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased LTP and recovered the PPF in deficient LTP of APPswe/PS1Δ9 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased dendritic protrusion morphogenesis, which was dependent on Rac activity. In addition, silencing of CDK5 increased BDNF expression, temporarily increased phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in neurites. Together, our data suggest that CDK5 downregulation induces synaptic plasticity in mature neurons involving Ca2+signaling and BDNF/CREB activation.
authors: Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia, Calle 62 # 52-59, Torre 1, Piso 4, Laboratorio 412, Medellín, Colombia.
authors: Rafael Andrés
authors: RA
authors: Posada-Duque
authors: Laboratory for Scientific Image Analysis (SCIAN-Lab), Center for Medical Informatics and Telemedicine (CIMT), Biomedical Neuroscience Institute BNI, ICBM, Universidad de Chile, Santiago, Chile.
authors: Omar
authors: O
authors: Ramirez
authors: Laboratory for Scientific Image Analysis (SCIAN-Lab), Center for Medical Informatics and Telemedicine (CIMT), Biomedical Neuroscience Institute BNI, ICBM, Universidad de Chile, Santiago, Chile.
authors: Steffen
authors: S
authors: Härtel
authors: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile.
authors: Nibaldo C
authors: NC
authors: Inestrosa
authors: Laboratory of Cell and Neuronal Dynamics, Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago, Chile.|Geroscience Center for Brain Health and Metabolism, Santiago, Chile.
authors: Felipe
authors: F
authors: Bodaleo
authors: Laboratory of Cell and Neuronal Dynamics, Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago, Chile.|Geroscience Center for Brain Health and Metabolism, Santiago, Chile.
authors: Christian
authors: C
authors: González-Billault
authors: Solomon H. Snyder Department of Neuroscience, Zanvyl-Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, USA.
authors: Alfredo
authors: A
authors: Kirkwood
authors: Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia, Calle 62 # 52-59, Torre 1, Piso 4, Laboratorio 412, Medellín, Colombia. patricia.cardonag@udea.edu.co.
authors: Gloria Patricia
authors: 0000-0002-3814-4494
authors: GP
authors: Cardona-Gómez
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism; D009473:Neuronal Plasticity; D010766:Phosphorylation; D017208:Rats, Wistar; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051360:Cyclin-Dependent Kinase 5
keywords: BDNF/CREB; CDK5 RNAi; Calcium; Dendritic protrusion morphogenesis; LTP; Synaptic plasticity