[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 233.2/C4
Topic: B.02.c. Nicotinic acetylcholine receptors: regulation and function
Support: ADCC pilot grant
Title: Pathophysiological levels of amyloid-beta 1-42 induces selective up-regulation of α7nAChRs
and cytotoxicity in differentiated SH-SY5Y cells
Authors: *Q. LIU 1 , S. EMADI 2 , M. SIERKS 2 , J. WU 1 ;
1 Neurol, Barrow Neurolog. Inst., Phoenix, AZ; 2 Chem. Engin., Arizona state university, phoenix,
AZ
Abstract: Dysfunction of basal forebrain cholinergic neurons (BFCNs) correlates with cognitive
deficits in Alzheimer disease (AD). Amyloid-beta (Aβ) 1-42, a major toxic peptide that
accumulates in the brain of AD patients, has been shown to directly interact with neuronal
nicotinic acetylcholine receptors (nAChRs) expressed on BFCNs. It remains unclear how Aβ
interacts with nAChRs expressed on BFCNs and modulates BFCN function. Our previous
studies indicated that pathophysiological levels of Aβ acutely blocked nAChRs on BFCNs, thus
affecting basal forebrain cholinergic transmission. In the present study, we investigated the
effects of 10 days exposure to Aβ on nAChRs expressed on differentiated cholinergic SH-SY5Y
cells. Molecular biology, electrophysiological, immunochemistry staining techniques, and LDH
(Lactic Dehydrogenase ) assay, were employed to perform this study. Our results revealed that
10 days exposure to Aβ selectively up-regulated α7-nAChR expression, which was accompanied
by a significant reduction in cell viability. After 10 days exposure to Aβ, function of α7-nAChRs
was comparable to non-treated α7-nAChRs, which was assessed by patch-clamp recordings in an
Aβ-containing environment. A significant increase in α7-nAChR function following Aβ
treatment was observed when cells were washed with Aβ-free medium. This up-regulation of α7containing
nAChRs could be a compensatory response to maintain cholinergic activity during
AD progression. Long-term interactions of α7-nAChRs with Aβ may serve as a pathogenic
mechanism of cholinergic neuronal dysfunction in AD.
Disclosures: Q. Liu , None; M. Sierks, None; J. Wu, None; S. Emadi, None.
Poster
233. Nicotinic Aacetylcholine Receptors: Regulation and Function II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 233.3/C5