PMID: 11923407Mar 30, 2002Paper

Noradrenergic depletion potentiates beta -amyloid-induced cortical inflammation: implications for Alzheimer's disease

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Michael T HenekaD L Feinstein

Abstract

Degeneration of locus ceruleus (LC) neurons and reduced levels of norepinephrine (NE) in LC projection areas are well known features of Alzheimer's disease (AD); however, the consequences of those losses are not clear. Because inflammatory mediators contribute to AD pathogenesis and because NE can suppress inflammatory gene expression, we tested whether LC loss influenced the brain inflammatory gene expression elicited by amyloid beta (Abeta). Adult rats were injected with the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4) to induce LC death and subsequently injected in the cortex with Abeta (aggregated 1-42 peptide). DSP4 treatment potentiated the Abeta-dependent induction of inflammatory nitric oxide synthase (iNOS), interleukin (IL)-1beta, and IL-6 expression compared with control animals. In contrast, the induction of cyclooxygenase-2 expression was not modified by DSP4 treatment. In control animals, injection of Abeta induced iNOS primarily in microglial cells, whereas in DSP4-treated animals, iNOS was localized to neurons, as is observed in AD brains. Injection of Abeta increased IL-1beta expression initially in microglia and at later times in astrocytes, and expression levels were greater in DSP...Continue Reading

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