Selective changes in expression of different nicotinic receptor subtypes in brain and adrenal glands of mice carrying human mutated gene for APP or over-expressing human acetylcholinestrase.
In this study, we investigated regulatory mechanisms and plasticity of the nicotinic acetylcholine receptors (nAChRs) in the brain and adrenal glands of two transgenic mice models over-expressing human beta-amyloid precursor protein (APP(SWE)Tg) and human AChE enzyme (hAChE-Tg), respectively. All animals were studied at 3 months of age. Binding studies showed higher (125)I-alpha-bungarotoxin (alpha7 nAChRs) and (3)H-epibatidine (alpha3 and alpha4 nAChRs) binding in the brain cortex and adrenal glands of hAChE-Tg mice compared to control mice. The APP(SWE)Tg mice showed a significantly lower relative level for the alpha4 mRNA in the brain cortex as well as a lower level of alpha3 mRNA, and higher level of alpha7 mRNA in the adrenal glands compared to control mice. A higher relative mRNA level of alpha3 and alpha4 nAChRs was observed in the brain as well as of alpha3 and alpha7 nAChRs in the adrenal glands of hAChE-Tg mice compared to control mice. Different nicotinic receptor plasticity is revealed in the brain cortex and adrenal glands in two transgenic mice models with different underlying pathophysiological mechanisms. Deposition of beta-amyloid (Abeta) may impair neurotransmitter activity in brain as well as in the adrenal gland.
Department of Neurotec, Division of Molecular Neuropharmacology, Karolinska Institute, Karolinska University Hospital, Huddinge B84, S-141 86 Stockholm, Sweden.
Malahat
M
Mousavi
Ivan
I
Bednar
Agneta
A
Nordberg
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011978:Receptors, Nicotinic / Q000145:classification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D016564:Amyloid beta-Protein Precursor; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D000110:Acetylcholinesterase