Survival and plasticity of basal forebrain cholinergic systems in mice transgenic for presenilin-1 and amyloid precursor protein mutant genes.
The basalo-cortical cholinergic system was characterized in mice expressing mutant human genes for presenilin-1 (PS1), amyloid precursor protein (APP), and combined PS/APP. Dual immunocytochemistry for ChAT and A beta revealed swollen cholinergic processes within cortical plaques in both APP and PS/APP brains by 12 months, suggesting aberrant sprouting or redistribution of cholinergic processes in response to amyloid deposition. At 8 months, cortical and subcortical ChAT activity was normal (PS/APP) or elevated (PS, APP frontal cortex), while cholinergic cell counts (nBM/SI) and receptor binding were unchanged. ChAT mRNA was up-regulated in the nBM/SI of all three transgenic lines at 8 months. The data indicate that the basal forebrain cholinergic system does not degenerate in mice expressing AD-related transgenes, even in mice with extreme amyloid load. The
Hernandez
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Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
Sugaya
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K
Qu
T
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McGowan
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E
Duff
K
K
McKinney
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M
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000201:enzymology / Q000254:growth & development / Q000473:pathology*; D002452:Cell Count; D002470:Cell Survival / Q000235:genetics*; D002540:Cerebral Cortex / Q000201:enzymology / Q000254:growth & development / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000002:abnormalities / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine