Expression of the alpha7, alpha4 and alpha3 nicotinic receptor subtype in the brain and adrenal medulla of transgenic mice carrying genes coding for human AChE and beta-amyloid.
Human AChE-enzyme (hAChE) enhances the over-expression of beta-amyloid (Abeta) containing plaques in the brain of transgenic mice (APP(SWE)/hAChE-Tg) carrying mutated genes for human amyloid precursor protein (APP(SWE)) and hAChE. In this study, we showed that interaction of hAChE with Abeta affects the plasticity of the alpha7 nicotinic acetylcholine receptors (nAChRs) both in the brain and adrenal medulla. An age-related increase in the (125)I-alphabungarotoxin ((125)I-alphaBTX) binding (specific to alpha7 nAChRs) was observed in the adrenal medulla of 3, 7 and 10 months old control mice. In contrast, a significant decrease in (125)I-alphaBTX binding was detected in the adrenal medulla of 10 months old APP(SWE)/hAChE-Tg. A significantly higher alpha7 nAChR mRNA level was observed in the brain of APP(SWE)/hAChE-Tg at 3 and 7 months of age and in the adrenal medulla at 3 and 10 months of age compared to those of the control mice. The alpha3 nAChR mRNA level was significantly higher in the brain of APP(SWE)/hAChE-Tg at 3 months of age and in the adrenal medulla at 10 months of age. The alpha4 nAChR mRNA level remained unchanged in the brain and adrenal medulla of APP(SWE)/hAChE-Tg for all age groups. Based on these observations, we conclude that a high load of Abeta and an over-expression of hAChE induce differences in the expression of the nAChR subtypes at various ages in the brain and in the adrenal medulla of hAChE/APP(SWE)Tg mice. The findings may have implications for a better understanding the underlying mechanism for AD-related pathogenesis.
Mousavi
Malahat
M
Karolinska Institute, Department of NEUROTEC, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, Novum 5th floor, S-14186 Stockholm, Sweden. malahat.mousavi@ki.se
Nordberg
Agneta
A
D000110:Acetylcholinesterase / Q000235:genetics*; D000313:Adrenal Medulla / Q000378:metabolism*; D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002038:Bungarotoxins / Q000493:pharmacokinetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D011978:Receptors, Nicotinic / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D002038:Bungarotoxins; D007456:Iodine Isotopes; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D000110:Acetylcholinesterase