Cellular and Molecular Life Sciences<\/p>\n\n\n\n
Rafael Andr\u00e9s Posada-Duque, Omar Ramirez, Steffen H\u00e4rtel, Nibaldo C Inestrosa, Felipe Bodaleo, Christian Gonz\u00e1lez-Billault, Alfredo Kirkwood, Gloria Patricia Cardona-G\u00f3mez<\/p>\n\n\n\n
ABSTRACT<\/strong>
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\u2014such as long-term potentiation (LTP)\u2014have 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\/PS1\u03949 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12\u00a0days 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+<\/sup>\u00a0signaling and BDNF\/CREB activation.<\/p>\n\n\n\n