Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in transgenic mice overexpressing human acetylcholinesterase.
Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits alpha4, beta2, and alpha7 were analysed in 3-mo-old transgenic mice generated with a neuronal overexpression of human acetylcholinesterase and in age-matched controls. The acetylcholinesterase transgenic mice display progressive cognitive impairment in spatial learning and memory. We here report a significantly increased [3H]epibatidine and [125I]alphabungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitativein situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits alpha4, beta2, and alpha7 in various brain regions in the transgenic mice compared to nontransgenic controls. Our results suggest that disruption of balanced cholinergic transmission by constitutive overexpression of acetylcholinesterase is accompanied by variable upregulation of several nicotinic receptor subtypes, in particular these associated with cholinergic terminals participating in compensatory response.
Svedberg
Marie M
MM
Karolinska Institutet, NEUROTEC, Division of Molecular Neuropharmacology, Huddinge University Hospital, Stockholm, Sweden. marie.svedberg@neurotec.ki.se
Svensson
Anne-Lie
AL
Johnson
Mary
M
Lee
Mandy
M
Cohen
Osnat
O
Court
Jennifer
J
Soreq
Hermona
H
Perry
Elaine
E
Nordberg
Agneta
A
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018722:Nicotinic Agonists / Q000378:metabolism; D021122:Protein Subunits; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic; D015854:Up-Regulation / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000110:Acetylcholinesterase; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D002091:Butyrylcholinesterase; D018722:Nicotinic Agonists; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C082748:epibatidine