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Alterations in cholinergic and non‐cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with β‐amyloid plaque pathology
Author(s) -
Klingner Margrit,
Apelt Jenny,
Kumar Ashok,
Sorger Dietlind,
Sabri Osama,
Steinbach Jörg,
Scheunemann Matthias,
Schliebs Reinhard
Publication year - 2003
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2003.08.001
Subject(s) - cholinergic , genetically modified mouse , endocrinology , medicine , neurotransmitter , alzheimer's disease , biology , amyloid precursor protein , acetylcholine , glutamate receptor , transgene , neuroscience , receptor , central nervous system , biochemistry , disease , gene
Abstract 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 β‐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 β‐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 β‐adrenergic as well 5‐HT 1A ‐ and 5‐HT 2A ‐receptor binding levels were hardly affected, whereas α 1 ‐ and α 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 β‐amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.