[Abstract Title]. - Society for Neuroscience

Tohoku Univ. Grad. Sch. of Pharmaceut. Sci., Sendai, Japan; 3 Dept. of Rehabil., Tohoku Bunka
Gakuen Univ. Sch. of Med. Sci. & Welfare, Sedai, Japan
Abstract: The Ca 2+ /calmodulin-dependent protein kinase (CaMK) cascade, consisting of
CaMKI, CaMKIV and CaMK kinase (CaMKK), is an evolutionally conserved Ca 2+ -triggered
signal transduction pathway that plays important roles for a variety of neuronal functions
including gene expression and synaptic plasticity. We have previously demonstrated distinct
gene expression of CaMKI, CaMKIV and CaMKK in the adult brain. In this study, to examine
the roles of this cascade in the hippocampal development, we first examined the gene expression
of each isoform of CaMKI, CaMKIV and CaMKK in the developing mouse hippocampus by in
situ hybridization histochemistry. In the adult hippocampus, CaMKIβ2 and δ are expressed at a
higher level than CaMKIα and γ. During the hippocampal development, the expression of
CaMKIβ2 mRNA in the dentate granule cell layer was progressively increased, whereas its
expression in the CA1-3 pyramidal cell layers was gradually decreased during the postnatal
development. CaMKIδ mRNA showed prominent expression in the CA1-3 pyramidal cell layers
already at embryonic day 18 (E18) with a progressive increase in its expression during the
postnatal development. CaMKIα and γ mRNA showed moderate to weak expression throughout
the hippocampal development. The expression of CaMKIV mRNA was already prominent in the
CA1-3 pyramidal cell layers at E18 and gradually increased with a peak around postnatal day 15.
The expression of CaMKKα mRNA was almost negligible during embryonic development and
gradually increased in the dentate granule cell layer after birth. CaMKKβ mRNA was already
expressed abundantly in the hippocampus at E15 and progressively increased in the CA1-3
pyramidal cell layers during the postnatal development. Finally, to examine the roles in the
dendritic development, we overexpresssed the kinase-dead mutants of CaMKI, CaMKIV and
CaMKK in primary hippocampal neurons. The overexpression of a kinase-dead mutant of
CaMKI reduced the average dendritic length without any significant changes in the number of
dendrites. In contrast, the overexpression of a kinase-dead mutant of CaMKIV and CaMKK
resulted in decreased number of dendrites without any effects on the average dendritic length.
STO-609, an inhibitor of CaMKK, treatment reduced the number of dendrites without any
effects on the average dendritic length. All these findings suggest that CaMKI and CaMKIV are
involved in distinct steps of dendritic formation of hippocampal neurons, namely dendritic
extension and initiation, respectively.
Disclosures: A. Kamata, None; K. Fukunaga, None; H. Kondo, None; H. Sakagami, None.
Poster
231. Dendrite Growth and Branching: Signaling
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 231.20/B33