Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.
Cholinergic deficits in Alzheimer's disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether beta-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17 months (moderate to high cortical beta-amyloid plaque load) were examined for a number of cholinergic and non-cholinergic markers. Transgenic mice with no significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to choline uptake sites in anterior brain regions as compared to non-transgenic littermates, while in aged transgenic mice with high number of plaque deposits decreased HCh-3 binding levels were accompanied by increased vesicular acetylcholine transporter binding in selected cortical brain regions. In aged transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5-HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral cortical regions as compared to non-transgenic littermates. The development of changes in both cholinergic and non-cholinergic markers in transgenic Tg2576 mouse brain already before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.
Klingner
Margrit
M
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany.
Apelt
Jenny
J
Kumar
Ashok
A
Sorger
Dietlind
D
Sabri
Osama
O
Steinbach
Jörg
J
Scheunemann
Matthias
M
Schliebs
Reinhard
R
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005790:General Adaptation Syndrome; D051379:Mice; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D009435:Synaptic Transmission; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D002794:Choline; D000109:Acetylcholine