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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 \u03b2 (A\u03b2). Adult rats were injected with the selective neurotoxin<jats:italic>N<\/jats:italic>-(2-chloroethyl)-<jats:italic>N<\/jats:italic>-ethyl-2 bromobenzylamine (DSP4) to induce LC death and subsequently injected in the cortex with A\u03b2 (aggregated 1\u201342 peptide). DSP4 treatment potentiated the A\u03b2-dependent induction of inflammatory nitric oxide synthase (iNOS), interleukin (IL)-1\u03b2, 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 A\u03b2 induced iNOS primarily in microglial cells, whereas in DSP4-treated animals, iNOS was localized to neurons, as is observed in AD brains. Injection of A\u03b2 increased IL-1\u03b2 expression initially in microglia and at later times in astrocytes, and expression levels were greater in DSP4-treated animals than in controls. The potentiating effects of DSP4 treatment on iNOS and IL-1\u03b2 expression were attenuated by coinjection with NE or the \u03b2-adrenergic receptor agonist isoproterenol. These data demonstrate that LC loss and NE depletion augment inflammatory responses to A\u03b2 and suggest that LC loss in AD is permissive for increased inflammation and neuronal cell death.<\/jats:p>","DOI":"10.1523\/jneurosci.22-07-02434.2002","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T22:30:10Z","timestamp":1523658610000},"page":"2434-2442","source":"Crossref","is-referenced-by-count":221,"title":["Noradrenergic Depletion Potentiates \u03b2-Amyloid-Induced Cortical Inflammation: Implications for Alzheimer's Disease"],"prefix":"10.1523","volume":"22","author":[{"given":"Michael T.","family":"Heneka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Galea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy","family":"Gavriluyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Dumitrescu-Ozimek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnna","family":"Daeschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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