Effect of beta-amyloid peptides on alpha-7 nicotinic receptor status in astrocytes and neurons, and its relationship to pathogenesis of Alzheimer's disease.
- Author:
Yan XIAO
1
;
Ke-ren SHAN
;
Zhi-zhong GUAN
Author Information
- Publication Type:Journal Article
- MeSH: Aged; Aged, 80 and over; Alzheimer Disease; genetics; metabolism; pathology; Amyloid beta-Peptides; chemistry; genetics; metabolism; Animals; Astrocytes; cytology; drug effects; metabolism; Brain; metabolism; pathology; Cell Line, Tumor; Cells, Cultured; Glial Fibrillary Acidic Protein; analysis; Humans; Immunoblotting; Immunohistochemistry; Male; Mice; Mutation; Neurons; cytology; drug effects; metabolism; Peptide Fragments; pharmacology; Receptors, Nicotinic; biosynthesis
- From: Chinese Journal of Pathology 2006;35(8):462-466
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the alterations of alpha-7 nicotinic receptor (nAChR) status in human brain tissues with Alzheimer's disease (AD) and mouse brain tissues with Swedish APP670/671 gene mutation, and to study the effect of beta-amyloid peptides (A-beta) on alpha-7 nAChR status in cultured astrocytes and neurons.
METHODSPostmortem brain tissues from patients with AD and mouse brain tissues with Swedish APP mutation were collected. The expression of alpha-7 nAChR on astrocytes and neurons was detected by immunohistochemistry (ABC method). The alpha-7 nAChR protein level was measured by Western blotting. On the other hand, cultured astrocytes and neurons were treated with different concentrations of A-beta 25 - 35. The alpha-7 nAChR protein level was then measured.
RESULTSIncreased number of astrocytes surrounding senile plaques was observed in AD brain tissues. In AD brain tissues, as compared to age-matched controls, alpha-7 nAChR protein level was increased in astrocytes, but decreased in neurons. High level of alpha-7 nAChR protein was also observed in mouse brain tissues with APP mutation. Exposure to A-beta 25 - 35 induced an increase (up to 38%) in alpha-7 nAChR protein level in astrocytes but a decrease (up to 32%) in neurons.
CONCLUSIONSDecrease in alpha-7 nAChR level in neurons may be related to the pathogenesis of AD, whereas an increased level of alpha-7 nAChR in astrocytes, as induced by excessive A-beta, may represent a compensatory neuroprotective response.
