Cyclin-Dependent Kinase 5 Regulates Dendritic Spine Formation and Maintenance of Cortical Neuron in the Mouse Brain

Naoki Mita, Xiaojuan He, Kodai Sasamoto, Tomohide Mishiba, Toshio Ohshima

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Cyclin-dependent kinase 5 (Cdk5) activity is dependent on its association with 1 of 2 neuron-specific activators, p35 or p39. Cdk5 and its activators play an important role in brain development as well as higher functions like synaptic plasticity, learning, and memory. Reduction in p35 was reported in postmortem schizophrenia brain, in which reduced dendritic spine density was observed. Previous in vitro experiments have shown that Cdk5 is involved in dendritic spine formation, although in vivo evidence is limited. We examined dendritic spine formation in inducible-p35 conditional knockout (p35 cKO); p39 KO mice. When we deleted the p35 gene either during early postnatal days or at adult stage, we observed reduced spine densities of layer V neurons in the cerebral cortex and CA1 pyramidal neurons in the hippocampus. We further generated CA1-specific p35 conditional knockout (CA1-p35 cKO) mice and also CA1-p35 cKO; p39 KO mice in which have specific deletion of p35 in the CA1 region of hippocampus. We found a greater reduction in spine densities in CA1 pyramidal neurons in CA1-p35 cKO; p39 KO mice than in CA1-p35 cKO mice. These results indicate that dendritic spine formation and neuronal maintenance are dependent on Cdk5 activity.

    Original languageEnglish
    Pages (from-to)967-976
    Number of pages10
    JournalCerebral Cortex
    Volume26
    Issue number3
    DOIs
    Publication statusPublished - 2016 Mar 1

    Keywords

    • Cdk
    • conditional knockout
    • dendritic spine
    • hippocampus

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Cognitive Neuroscience

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