ISSN:
1573-6903
Keywords:
Amyloid peptide
;
antioxidants
;
trans-ACPD
;
carbachol
;
cytosolic free calcium concentration
;
Ins(1,4,5)P3
;
cortical neuronal culture
;
B27 supplement
;
neurodegeneration
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Signal transduction systems, including cholinergic pathways, which are likely to be of pathophysiological significance are altered in Alzheimer's disease (AD). Muscarinic cholinergic receptors are linked to the hydrolysis of phosphoinositide, involving the production of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] and the mobilization of cytosolic free calcium concentrations ([Ca2+]i). Effects of amyloid peptide (Aβ) on these signals prior to neuronal degeneration were examined in cultured rat cortical cells. Aβ increased the release of lactate dehydrogenase (LDH) in a concentration-dependent manner, however, it was blocked by B27 supplement. Prolonged exposure to a sublethal dose of Aβ 25–35 or 1–42 disrupted carbachol-mediated release of Ins(1,4,5)P3 and [Ca2+]i, which was inhibited in media supplemented with B27 or the antioxidant vitamin E. In order to determine the specificity of the effect of Aβ, various agonists glutamate or KCl but not bradykinin which utilize the phosphoinositide cascade were investigated. Our results indicated that Aβ did not affect the stimulation of glutamate or KCl-mediated production of Ins(1,4,5)P3 or cause elevation in [Ca2+]i. Furthermore, metabotropic agonist trans-1-amino-cyclopentane-1,3,-dicarboxylate (ACPD) elevated calcium level was not inhibited by Aβ pretreatment. Taken together, the results demonstrate that a sublethal dose of Aβ selectively impaired cholinergic receptor-mediated signal transduction pathways, and antioxidant or B27 supplement attenuated this effect of Aβ. Alterations of cholinergic signaling by prolonged exposure to Aβ could be involved in cortical neurodegeneration that occurs in AD. Because functional loss of cholinergic pathways is an important aspect of AD, the differences in susceptibility of these two types of receptors prior to other signs of Aβ action is important and requires further investigation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007592007956
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