Hippocampal spine changes across the sleep–wake cycle: corticosterone and kinases

    1. Suguru Kawato1,2,4
    1. 1Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3‐8‐1 Komaba, Meguro‐ku, Tokyo 152-8902, Japan
      2Bioinformatics Project of Japan Science and Technology Agency, University of Tokyo, Tokyo, Japan
      3Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sports Sciences, University of Tsukuba, 1‐1‐1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
      4Department of Urology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Tokyo 113-8424, Japan
    1. Correspondence should be addressed to S Kawato; Email: kawato{at}bio.c.u-tokyo.ac.jp


    The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive to CORT, since glucocorticoid receptors are highly expressed. In rat hippocampus fixed in a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased upon waking (within 3 h), as compared with the spine density in the sleep state. Particularly, the large-head spines increased. The observed change in the spine density may be due to the change in the hippocampal CORT level, since the CORT level at awake state (∼30 nM) in cerebrospinal fluid was higher than that at sleep state (∼3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT into ADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks.

    • Received in final form 14 May 2015
    • Accepted 1 June 2015
    • Made available online as an Accepted Preprint 1 June 2015
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