Selective nicotinic receptor consequences in APP(SWE) transgenic mice.
The nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors and acetylcholinesterase (AChE) activity were studied in the brains of APP(SWE) transgenic mice (Tg+) and age-matched nontransgenic controls (Tg-) that were between 4 and 19 months of age. A significant increase in the binding of 125I-labeled alpha-bungarotoxin (alpha7 nAChRs) was observed in most brain regions analyzed in 4-month-old Tg+ mice, preceding learning and memory impairments and amyloid-beta (Abeta) pathology. The enhanced alpha7 receptor binding was still detectable at 17-19 months of age. Increase in [3H]cytisine binding (alpha4beta2 nAChRs) was measured at 17-19 months of age in Tg+ mice, at the same age when the animals showed heavy Abeta pathology. No significant changes in [3H]pirenzepine (M1 mAChRs) or [3H]AFDX 384 (M2 mAChRs) binding sites were found at any age studied. The upregulation of the nAChRs probably reflects compensatory mechanisms in response to Abeta burden in the brains of Tg+ mice.
Bednar
Ivan
I
Divisions of Molecular Neuropharmacology, Occupational Therapy and Elderly Care Research (NEUROTEC), S-141 86 Stockholm, Sweden.
Paterson
David
D
Marutle
Amelia
A
Pham
Therese M
TM
Svedberg
Marie
M
Hellström-Lindahl
Ewa
E
Mousavi
Malahat
M
Court
Jennifer
J
Morris
Christopher
C
Perry
Elaine
E
Mohammed
Abdul
A
Zhang
Xiao
X
Nordberg
Agneta
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C579166:Chrna7 protein, mouse; D010446:Peptide Fragments; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000110:Acetylcholinesterase