[Abstract Title]. - Society for Neuroscience

location was predominantly nuclear. Thus, the shift of pS214 from the nucleus to the cytoplasm
is tightly correlated with disease. In culture, we observed strong nuclear pS214 staining in mouse
and human neuroblastoma cells but only during mitosis. On the other hand, clear nuclear pS214
staining was found in many cultured mouse cortical neurons, even with no detectable
chromosome condensation. The pS214-stained neurons had well defined nuclei and were
activated caspase 3-negative. We speculated that DNA damage might serve as a trigger for the
cytoplasmic shift of pS214, so N2a neuroblastoma cells were exposed to γ-rays to induce DNA
breaks. Nuclear foci of H2AX staining quickly formed in treated cells while cytoplasmic pS214
staining increased, eventually coalescing into distinct aggregates that grew in size over time.
Taken together, our data suggest that tau, and it pS214 isoform may play an unexpected role in
the DNA damage response system of a neuron.
Disclosures: J. Chen, None; M. Martinez-Lage, None; J.Q. Trojanowski , None; K. Herrup,
None; H. Li, None.
Poster
245. Tau and Alzheimer's disease
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 245.16/O10
Topic: C.01.h. Tau
Title: In vitro neuroprotection by α 7 nAChR ligands: analysis of effects on Aβ 1-42-induced
neurite outgrowth and tau phosphorylation
Authors: *M. HU, M. E. SCHURDAK, P. S. PUTTFARCKEN, R. EL KOUHEN, M.
GOPALAKRISHNAN, J. F. WARING, J. LI;
Abbott Labs., Abbott Park, IL
Abstract: Alzheimer‟s disease is an age-related neurodegenerative disorder characterized by
progressive loss of memory accompanied with cholinergic neurodegeneration. There is
substantial evidence indicating that Aβ1-42 is one of the major factors in AD pathogenesis, but the
underlying mechanism(s) remains unclear. In this study, we first established an in vitro model of
Aβ1-42-induced neurotoxicity in rat neonatal primary cortical cells, using high content screen
(HCS) microscopy for measurement of neurite outgrowth, to address the neurotoxicity effect of
Aβ1-42. Neurite outgrowth was found to be significantly reduced by Aβ1-42 (300 nM - 30 µM), but
not by the scrambled control peptide control, in a time- and concentration-dependent manner.
The total number of neurons was not affected. The Aβ1-42-induced reduction of neurite outgrowth
was partially attenuated by α7 nicotinic acetylcholine receptor (nAChR) selective agonist PNU-
282987 and also by the antagonist methyllycaconitine (MLA). This suggested that the observed