[Effect of beta-amyloid peptides on alpha-7 nicotinic receptor status in astrocytes and neurons, and its relationship to pathogenesis of Alzheimer's disease].
OBJECTIVE
To 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.


METHODS
Postmortem 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.


RESULTS
Increased 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.


CONCLUSIONS
Decrease 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.
Xiao
Yan
Y
Department of Molecular Biology, Guiyang Medical College, Guiyang 550004, China.
Shan
Ke-ren
KR
Guan
Zhi-zhong
ZZ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000096:biosynthesis*
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D011978:Receptors, Nicotinic