Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 47, Issue 4, Pages 281-290Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2005.04.023
Keywords
Alzheimer's disease; calcium channel; cholinergic receptors; mRNA; rat brain
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Neuronal nicotinic acetylcholine receptors (nAChRs) are thought to be involved in the pathogenesis of Alzheimer's disease (AD). Interestingly, in the brains of patients with this disease, losses of several subtypes of nAChRs on neurons have been reported, while an increase in alpha 7 nAChRs was recently detected in the astrocytes. However, little is presently known about the expressions of individual subunits of nAChR on rat astrocytes in primary culture or the possible influence of exposure to P-amyloid peptide (A beta), a neuropathological hallmark of AD, on this expression. Thus, in the present investigation the levels of individual nAChR subunits on primary rat astrocytes and the possible direct influence of A beta s on the receptors were examined by RT-PCR, Western blotting, monitoring intracellular free calcium and immumohistochemistry. The alpha 4, alpha 7, beta 2 and beta 3 subunits and related calcium channel responses were found in these cells, whereas neither alpha 2 nor alpha 3 could be detected. Elevation in the levels of alpha 7, alpha 4 and beta 2 mRNAs and proteins were observed in astrocytes exposed to 0.1-100 nM A beta(1-42). In contrast, incubation with 1 mu M A beta(1-42) or A beta(35-25) did not affect these levels. We propose that the enhanced expression of alpha 7, alpha 4 and beta 2 nAChRs by astrocytes stimulated directly by nanomolar concentrations of A beta(1-42) might be related to ongoing defensive or compensative mechanisms. (c) 2005 Elsevier Ltd. All rights reserved.
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