期刊
JOURNAL OF CHEMICAL NEUROANATOMY
卷 40, 期 1, 页码 63-70出版社
ELSEVIER
DOI: 10.1016/j.jchemneu.2010.03.005
关键词
B-max; GPCR; Functional activity; MCI; Muscarinic receptor
资金
- [TGA000257]
- [PO1AG14449]
- [P50AG10161]
Although the M-1 muscarinic receptor is a potential therapeutic target for Alzheimer's disease (AD) based on its wide spread distribution in brain and its association with learning and memory processes, whether its receptor response is altered during the onset of AD remains unclear. A novel [S-35]GTP gamma S binding/immunocapture assay was employed to evaluated changes in M-1 receptor function in cortical tissue samples harvested from people who had no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD. M-1 function was stable across clinical groups. However,[H-3]-oxotremorine-M radioligand binding studies revealed that the concentration of M-1 cortical receptors increased significantly between the NCI and AD groups. Although M-1 receptor function did not correlate with cognitive function based upon mini-mental status examination (MMSE) or global cognitive score (GCS), functional activity was negatively correlated with the severity of neuropathology determined by Braak staging and NIA-Reagan criteria for AD. Since M-1 agonists have the potential to modify the pathologic hallmarks of AD, as well as deficits in cognitive function in animal models of this disease, the present findings provide additional support for targeting the M, receptor as a potential therapeutic for AD. (C) 2010 Elsevier B.V. All rights reserved.
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