γ-Aminobutyric acid type a receptor inhibition triggers a nicotinic neuroprotective mechanism

Ferchmin, P. A., Pérez, D., Castro Alvarez, W., Penzo, M. A., Maldonado, H. M., Eterovic, V. A. (2013) γ-Aminobutyric acid type a receptor inhibition triggers a nicotinic neuroprotective mechanism. Journal of Neuroscience Research, 91 (3). pp. 416-425. ISSN 03604012

URL: http://www.ncbi.nlm.nih.gov/pubmed/23280428
DOI: 10.1002/jnr.23155

Abstract

Nicotinic acetylcholine receptor (nAChR)-mediated neuroprotection has been implicated in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases and hypoxic ischemic events as well as other diseases hallmarked by excitotoxic and apoptotic neuronal death. Several modalities of nicotinic neuroprotection have been reported. However, although this process generally involves α4β2 and α7 subtypes, the underlying mechanisms are largely unknown. Interestingly, both activation and inhibition of α7 nAChRs have been reported to be neuroprotective. We have shown that inhibition of α7 nAChRs protects the function of acute hippocampal slices against excitotoxicity in an α4β2-dependent manner. Neuroprotection was assessed as the prevention of the N-methyl-D-aspartate-dependent loss of the area of population spikes (PSs) in the CA1 area of acute hippocampal slices. Our results support a model in which α7 AChRs control the release of γ-aminobutyric acid (GABA). Blocking either α7 or GABA(A) receptors reduces the inhibitory tone on cholinergic terminals, thereby promoting α4β2 activation, which in turn mediates neuroprotection. These results shed light on how α7 nAChR inhibition can be neuroprotective through a mechanism mediated by activation of α4β2 nAChRs.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > GABA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor
CSHL Authors:
Communities: CSHL labs > Li lab
CSHL Post Doctoral Fellows
Depositing User: Matt Covey
Date: 2013
Date Deposited: 30 Jan 2013 21:15
Last Modified: 03 May 2013 13:36
Related URLs:
URI: https://repository.cshl.edu/id/eprint/26941

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