[Abstract Title]. - Society for Neuroscience

constructs, we studied mechanism for regulating GSK3β gene expression in neuron under
differentiating condition. SH-SY5Y, a human neuroblastoma cell, stably expressing luciferase
gene directed by GSK3β promoter was treated with retinoic acid (RA). Luciferase activity in SH-
SY5Y cells was increased by RA treatment. This RA-induced activation of the promoter was
confirmed by RT-PCR for endogenous GSK3β mRNA of SH-SY5Y cells. On the contrary, the
RA-induced activation was not observed in HEK293, a human embryonic kidney cell. Because
the effect of RA was enhanced by depolarization induced by high K+, the neuron specific RAinduced
activation of GSK3β expression might be depended on activity of neuronal cells.
Recently it has been reported that RA enhanced the protein level of GSK3β resulting in AD
linked phosphorylation of tau in SH-SY5Y cells (Jamsa, A. et al., 2004). This phosphorylation
was inhibited by lithium chloride a GSK3β inhibitor. In our study, lithium reduced the RAinduced
activation of GSK3β promoter. Thus, inhibition of tau phosphorylation by lithium may
be based on modifying not only the kinase activity but also transcription of GSK3β. Our results
may promote to develop a new therapeutic agent for treating AD or related disorders.
Disclosures: O. Murayama, None; A. Sumikura, None; S. Nakanishi, None; Y. Sasaki,
None; M. Matsuda, None.
Poster
245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 245.18/O12
Topic: C.01.h. Tau
Support: NIH AG026252
N. Bud Grossman Ctr for Memory Research and Care Fund
NIH NS033249
Title: The effect of tau phosphorylation on dendritic spine morphology in rodent hippocampal
and cortical neurons
Authors: *B. R. HOOVER 1 , K. H. ASHE 2 , D. LIAO 3 ;
1 N Bud Grossman Ctr. Dept Neurol, 2 N Bud Grossman Ctr, Dept Neurol, GRECC, VAMC,
3 Dept Neurosci., Univ. Minn, Minneapolis, MN
Abstract: Tau is a major microtubule-binding protein localized primarily to neuronal axons. In
the axons of healthy neurons, tau acts to stabilize microtubules and promote their assembly in the