[Abstract Title]. - Society for Neuroscience

subcellular locations and therefore different molecules on hippocampal neurons (St. John, 2007).
A large and growing body of evidence indicates that the rapid trafficking of glutamate receptors
onto and off of the neuronal surface plays a critical role in important forms of synaptic plasticity.
It has been suggested that Aβ peptides interfere with synaptic plasticity - and possibly cause
memory deficits in AD - by altering the normal dynamics of glutamate receptor trafficking in
CNS neurons. We have examined the effects of different assembly forms of Aβ42 on the
endocytosis of AMPA-type glutamate receptor subunits in cultured hippocampal neurons, using
microscopic imaging to track and localize the internalized receptors (St. John and Gordon, 2001).
Our results to date indicate that Aβ42 alters the constitutive endocytosis of GluR1 and GluR2
subunits, even though it does not appear to bind to those receptors. Experiments in progress are
examining the effects of Aβ42 on agonist-induced trafficking of glutamate receptors and
comparing the effects of different Aβ42 assembly forms on glutamate receptor dynamics in these
neurons.
Disclosures: P.A. St John , None.
Poster
244. Abeta Toxicity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 244.13/M6
Topic: C.01.c. Abeta toxicity
Support: BRNI Institute support
NIH National Cancer Institute (CA31845)
Title: A cellular model for Alzheimer‟s disease therapeutic efficacy: PKC activator bryostatin
and a synthetic analog reverse Aβ toxicity on cultured fibroblasts
Authors: *T. K. KHAN 1 , T. J. NELSON 1 , V. A. VERMA 2 , P. A. WENDER 2,3 , D. L. ALKON 1 ;
1 Memory division, B Rockefeller Neurosci Institu, Morgantown, WV; 2 Chem., 3 Chem. and
Systems Biol., Stanford Univ., Stanford, CA
Abstract: PKC signaling deficits may themselves contribute to the origins of Alzheimer‟s
disease (AD). Bryostatin, a potent PKC activator, has the potential to ameliorate both the
neurodegeneration and the recent memory loss of AD. Bryostatin and a synthetic analog
(picolog) were found to cause stimulation of non-amyloidogenic pathways by increasing αsecretase
activity and thus lowering the amount of toxic Aβ1-42 produced. In the range of subnanomolar
to nanomolar concentrations, both bryostatin and picolog, increased the secretion of