β-Amyloid induced effects on cholinergic, serotonergic, and dopaminergic neurons is differentially counteracted by anti-inflammatory drugs.
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| Abstract |
β-Amyloid (Aβ) is a small peptide that plays a potent role in synaptic plasticity as well as forms amyloid plaques in Alzheimer's disease (AD). Recent studies suggest that Aβ deposition is deleterious not only in AD, but also in Parkinson's disease (PD) and depression. This Aβ effect is associated with inflammatory processes. However, further evaluation is needed to understand how Aβ and inflammation interact and contribute to the regulation of the cholinergic, serotonergic, and dopaminergic neuronal populations. The aim of the present study was to investigate the effects of Aβ(1-42) on cholinergic neurons of the nucleus basalis of Meynert (which degenerate in AD), on serotonergic neurons of the dorsal raphe nucleus (which play a role in depression), and on dopaminergic neurons of the ventral mesencephalon (which degenerate in PD) in rat organotypic brain slices. Furthermore, we investigated whether anti-inflammatory drugs (celecoxib, citalopram, cyclooxygenase-2 inhibitor, ibuprofen, indomethacin, piclamilast) modulate or counteract Aβ-induced effects. Two-week-old organotypic brain slices of the nucleus basalis of Meynert, dorsal raphe nucleus, and ventral mesencephalon were incubated with 50 ng/ml Aβ(1-42) with or without anti-inflammatory agents for 3 days. Our results reveal that Aβ significantly decreased the number of choline acetyltransferase-positive cholinergic, tryptophan hydroxylase-positive serotonergic, and tyrosine hydroxylase-positive dopaminergic neurons and that anti-inflammatory drugs partially counteracted the Aβ-induced neuronal decline. This decline was not due to apoptotic processes (as evaluated by TUNEL, propidium iodide, caspase), oxidative stress (as measured by nitrite, catalase, or superoxide dismutase-2), or inflammation, but was most likely caused by a downregulation of these key enzymes.
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| Authors | Tanja Hochstrasser, Lindsay A Hohsfield, Barbara Sperner-Unterweger, Christian Humpel |
| Journal | Journal of neuroscience research (J Neurosci Res) Vol. 91 Issue 1 Pg. 83-94 (Jan 2013) ISSN: 1097-4547 [Electronic] United States |
| PMID | 22996751 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2012 Wiley Periodicals, Inc. |
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