Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease

Agarwal, Smriti, Tannenberg, Rudi K. and Dodd, Peter R. (2008) Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease. Journal of Alzheimer's Disease, 14 3: 313-321.


Author Agarwal, Smriti
Tannenberg, Rudi K.
Dodd, Peter R.
Title Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease
Journal name Journal of Alzheimer's Disease   Check publisher's open access policy
ISSN 1387-2877
1875-8908
Publication date 2008-01-01
Sub-type Article (original research)
Open Access Status Not Open Access
Volume 14
Issue 3
Start page 313
End page 321
Total pages 9
Editor G. Perry
M. A. Smith
Place of publication Amsterdam, Netherlands
Publisher I O S Press
Language eng
Subject 1109 Neurosciences
Abstract Excitotoxicity may contribute to neuronal and synaptic loss in Alzheimer’s disease (AD). Aberrant levels of gephyrin, a post-synaptic receptor-stabilizing protein, could affect the inhibitory modulation of excitatory impulses. We assayed gephyrin protein in two brain areas susceptible to neuronal loss in AD, and in a spared area, in autopsy tissue from normal subjects (n = 15) and AD patients (n = 15). Quantification was by in-gel immunodetection against known concentrations of a recombinant truncated gephyrin standard. Gephyrin abundance was significantly reduced (P < 0.01) in AD. Area-wise analysis showed that gephyrin levels were reduced in both spared and susceptible regions, indicating a global phenomenon. When samples were categorized on an index of pathological severity, gephyrin levels decreased with increasing severity until a moderate index was reached, and then increased, suggesting that higher gephyrin levels might compensate for excitotoxic damage in late stages of the disease. AD males showed a more pronounced reduction in gephyrin levels than AD females cf same-sex controls. A major splice variant of gephyrin was detected in all cases and in all three brain areas. This is the first study of gephyrin expression in AD.
Keyword Excitotoxicity
Human brain
Inhibitory neurotransmission
Pathogenesis
Post-synaptic scaffold
Protein expression
Protein quantification
Synaptic remodeling
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Science Publications
Excellence in Research Australia (ERA) - Collection
 
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Created: Thu, 03 Sep 2009, 19:43:56 EST by Mr Andrew Martlew on behalf of Faculty of Science