title: Soluble beta amyloid evokes alteration in brain norepinephrine levels: role of nitric oxide and interleukin-1.
abstract: Strong evidence showed neurotoxic properties of beta amyloid (Aβ) and its pivotal role in the Alzheimer's disease (AD) pathogenesis. Beside, experimental data suggest that Aβ may have physiological roles considering that such soluble peptide is produced and secreted during normal cellular activity. There is now suggestive evidence that neurodegenerative conditions, like AD, involve nitric oxide (NO) in their pathogenesis. Nitric oxide also possess potent neuromodulatory actions in brain regions, such as prefrontal cortex (PFC), hippocampus (HIPP), and nucleus accumbens (NAC). In the present study, we evaluated the effect of acute Aβ injection on norepinephrine (NE) content before and after pharmacological manipulations of nitrergic system in above mentioned areas. Moreover, effects of the peptide on NOS activity were evaluated. Our data showed that 2 h after i.c.v. soluble Aβ administration, NE concentrations were significantly increased in the considered areas along with increased iNOS activity. Pre-treatment with NOS inhibitors, 7-Nitroindazole (7-NI), and N6-(1-iminoethyl)-L-lysine-dihydrochloride (L-NIL), reversed Aβ-induced changes. Ultimately, pharmacological block of interleukin1 (IL-1) receptors prevented NE increase in all brain regions. Taken together our findings suggest that NO and IL-1 are critically involved in regional noradrenergic alterations induced by soluble Aβ injection.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Morgese
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy ; Department of Pathology and Immunology, University of Geneva Geneva, Switzerland.
authors.forename: Marilena
authors.initials: M
authors.lastname: Colaianna
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy ; Department of Physiology and Pharmacology, La Sapienza, University of Rome Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mhillaj
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Zotti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavone
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Palma
authors.initials: P
authors.lastname: D'Antonio
authors.affiliation: Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences and Trinity College Institute of Neuroscience, Trinity College Dublin Dublin, Ireland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harkin
authors.affiliation: Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences and Trinity College Institute of Neuroscience, Trinity College Dublin Dublin, Ireland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gigliucci
authors.affiliation: Department of Physiology and Pharmacology, La Sapienza, University of Rome Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Section of Biomedical Sciences and Technologies, Department of Science, University "Roma Tre," Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
authors.affiliation: Department of Bio Agro-Food Sciences, The Institute of Sustainable Plant Protection, National Research Council Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: De Stradis
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tucci
authors.affiliation: Department of Physiology and Pharmacology, La Sapienza, University of Rome Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Trabace
keywords: hippocampus; interleukin-1; nitric oxide; norepinephrine; nucleus accumbens; prefrontal cortex; soluble beta amyloid