soluble beta amyloid evokes alteration in brain norepinephrine levels: role of nitric oxide and interleukin-1

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ID: 215354
2015
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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 hours 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.
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emorgese2015frontierssoluble Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Maria Grazia eMorgese;Marilena eColaianna;Emanuela eMhillaj;Margherita eZotti;Stefania eSchiavone;Palma eD'Antonio;Andrew eHarkin;Valentina eGigliucci;Patrizia eCampolongo;Viviana eTrezza;Angelo eDe Stradis;Paolo eTucci;Vincenzo eCuomo;Luigia eTrabace
Journal Journal of enzyme inhibition and medicinal chemistry
Year 2015
DOI
10.3389/fnins.2015.00428
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