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 Malahat Mousavi, Ivan Bednar, Agneta Nordberg * Department of Neurotec, Division of Molecular Neuropharmacology, Karolinska Institute, Karolinska University Hospital, Huddinge B84, S-141 86 Stockholm, Sweden Received 24 June 2004; accepted 12 July 2004 Abstract 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 b-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-a-bungarotoxin (a7 nAChRs) and 3 H-epibatidine (a3 and a4 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 a4 mRNA in the brain cortex as well as a lower level of a3 mRNA, and higher level of a7 mRNA in the adrenal glands compared to control mice. A higher relative mRNA level of a3 and a4 nAChRs was observed in the brain as well as of a3 and a7 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 b-amyloid (Ab) may impair neurotransmitter activity in brain as well as in the adrenal gland. # 2004 ISDN. Published by Elsevier Ltd. All rights reserved. Keywords: Brain; Cerebral cortex; Adrenal gland; RT–PCR; a3, a4, a7 nicotinic receptor; Transgenic mice; AChE; b-amyloid; APP SWE 1. Introduction Alzheimer’s disease (AD) is one of the most common types of dementia characterized by a progressive decline of cognitive function. Intracellular neurofibrillary tangles and extracellular neuritic senile plaques are recognized as two distinctive neuro-pathological features in AD postmortem brains. The plaques contain amyloid peptide fibrils consist- ing of b-amyloid (Ab). The cholinergic neurotransmission is impaired in AD with impairment of the nicotinic acet- ylcholine receptors (nAChRs) in the hippocampus and cerebral cortex of AD patients (Nordberg, 2001; Paterson and Nordberg, 2000). The nAChRs belong to a family of ligand-gated ion channels with a pentameric structure. Pre- sently, seven a (a2–a10) and three b (b2–b4) subunits of the nAChRs have been identified and cloned (Paterson and Nordberg, 2000; Sargent, 2000). The nAChRs are involved in the regulation of neuronal networks not only in the brain but also in peripheral nervous tissue including adrenal medulla, where they regulate the secretion of the stress hormones epinephrine and norepinephrine. We have recently characterized the expression of nAChR subtypes in the adrenal medulla both in rodent and human at different ages (Mousavi et al., 2001). A double mutation at codon 670/671 on the amyloid precursor protein (APP) gene on chromosome 21, the Swed- ish mutation (Mullan et al., 1992), alters the APP metabo- lism in the human brain, resulting in an over-expression of Ab causing early-onset familial AD. Mice carrying this mutated gene (APP SWE Tg) develop memory and learning deficits (Hsiao et al., 1996), aggressive behavior (Moechars www.elsevier.com/locate/ijdevneu Int. J. Devl Neuroscience 22 (2004) 545–549 * Corresponding author. Tel.: +46 8 585 85467; fax: +46 8 689 9210. E-mail address: Agneta.Nordberg@neurotec.ki.se (A. Nordberg). 0736-5748/$30.00 # 2004 ISDN. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijdevneu.2004.07.005