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• W2094788265 abstract "Degeneration of locus ceruleus (LC) neurons and subsequent reduction of norepinephrine (NE) in LC projection areas represent an early pathological indicator of Alzheimer's disease (AD). In order to study the effects of NE depletion on cortical and hippocampal adrenergic system changes, LC degeneration was induced in 3-month-old APP/PS1 mice by the neurotoxin N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4). Dsp4 induced a widespread loss of norepinephrine transporter binding in multiple brain structures already at 4.5 months. This was accompanied by changes of α-1-, α-2-, and β-1-adreneroceptor binding sites as well as altered adrenoceptor mRNA expression. In parallel, we observed increased micro- and astrogliosis in cortical and hippocampal structures in dsp4-treated groups. In addition, the expression of the pro-inflammatory cytokines CCL2 and IL-1β were induced in both, dsp4-treated and APP/PS1-transgenic mice, whereas IL-1α was only up-regulated in dsp4-treated APP/PS1 mice. Concerning amyloid β (Aβ) deposition, we observed an elevation of Aβ1-42 levels in aged dsp4-treated APP/PS1 mice. These data support the hypothesis that LC degeneration leads to dysregulation of adrenergic receptors and exacerbation of Aβ-induced neuroinflammation, both of which are exploitable for early disease marker development. ▶Locus ceruleus (LC) degeneration is an early event during Alzheimer's disease. ▶The LC provides noradrenergic innervation of the brain. ▶LC loss changes adrenoreceptor expression in its projection areas. ▶LC destruction causes increased chemokine production and micro- and astrogliosis. ▶Loss of the LC increases Aβ1-42 levels in aged APP/PS1 mice." @default.
• W2094788265 created "2016-06-24" @default.
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• W2094788265 date "2011-03-01" @default.
• W2094788265 modified "2023-10-16" @default.
• W2094788265 title "Distinct adrenergic system changes and neuroinflammation in response to induced locus ceruleus degeneration in APP/PS1 transgenic mice" @default.
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• W2094788265 doi "https://doi.org/10.1016/j.neuroscience.2010.11.052" @default.
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