Abstract
A large body of evidence suggests the importance of inflammation and oxidative or nitrosative stress in Alzheimer's disease (AD) pathogenesis. Inflammatory stimuli upregulate transcription of inducible nitric oxide synthase (iNOS), which can lead to the production of nitric oxide and other reactive nitrogen species. We previously found that genetic deletion of iNOS in mice overexpressing the amyloid precursor protein (APP) and presenilin-1 (PS1) reduced mortality, nitrosative stress, amyloid plaque burden, microgliosis, astrocytosis, and peri-plaque tau phosphorylation. We therefore examined the effects of N6-(1-iminoethyl)-L-lysine (L-NIL), a pharmacological iNOS inhibitor, or d-NIL, its enantiomeric control, in a transgenic mouse model of amyloid deposition. Tg19959 mice carry human APP with two mutations and develop amyloid plaques and memory impairment starting at 3-4 months of age. Mice were given L-NIL or D-NIL in the drinking water from 1 month of age and assessed behaviorally and histopathologically at 8 months of age. We found that L-NIL administration reduced disinhibition in the elevated plus maze, improved spatial memory performance in the Morris water maze, and decreased cortical amyloid deposition as well as micro...Continue Reading
References
Sep 1, 1992·Annals of Neurology·T M DawsonS H Snyder
Nov 11, 1994·Journal of Medicinal Chemistry·W M MooreM G Currie
Dec 29, 1995·European Journal of Pharmacology·S StengerC Bogdan
May 16, 1998·Biochemistry·R Bryk, D J Wolff
Aug 8, 1998·European Journal of Pharmacology·D J WolffM J Neulander
Nov 24, 1999·Journal of Neuropathology and Experimental Neurology·S C LeeD W Dickson
Aug 25, 2000·Journal of Psychopharmacology·A L ValeS Shafi
Mar 30, 2001·The Journal of Biological Chemistry·M A ChishtiD Westaway
Aug 7, 2001·British Journal of Pharmacology·A LawR Quirion
Jul 8, 2003·Molecular Neurobiology·Guy C Brown, Anna Bal-Price
May 19, 2004·Journal of Neurochemistry·Feng LiGunnar K Gouras
Sep 8, 2004·Neurobiology of Disease·Richard C LiDavid Gozal
Sep 29, 2004·Neuroscience·J RodrigoA P Fernández
Sep 29, 2004·Brain Research·M DumontR Lalonde
Dec 8, 2004·Behavioural Brain Research·Elisa OgnibeneGiovanni Laviola
May 3, 2005·Behavioural Brain Research·Lynn A HydeGuy A Higgins
Aug 24, 2005·Progress in Neurobiology·F X GuixF J Muñoz
Oct 26, 2005·Neuropharmacology·G LouinM Jafarian-Tehrani
Sep 9, 2006·Journal of Neurotrauma·Caroline GahmTiit Mathiesen
Sep 21, 2007·Nature Reviews. Neuroscience·Vittorio CalabreseAnna Maria Giuffrida Stella
May 20, 2008·Brain Research·Chiho Hirata-FukaeYasuji Matsuoka
Jul 22, 2008·Brain Research·M UdayabanuAnju Katyal
Aug 30, 2008·Neuroscience·Y Abu-GhanemY Amitai
Sep 6, 2008·Learning & Memory·Stephanie DaumasRichard G M Morris
Jan 6, 2009·Neurochemistry International·Konstantin YenkoyanMichael Aghajanov
May 19, 2009·Neuroscience·V EcheverriaG W Arendash
Citations
Aug 28, 2012·Human Molecular Genetics·Magali DumontM Flint Beal
Aug 10, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Magali DumontFlint Beal
Aug 17, 2010·PLoS Pathogens·Sheetal GandotraSabine Ehrt
Feb 22, 2014·Human Molecular Genetics·Cliona StackMagali Dumont
Mar 1, 2012·Neuroscience and Biobehavioral Reviews·R LalondeC Strazielle
Dec 7, 2010·Free Radical Biology & Medicine·Magali Dumont, M Flint Beal
Sep 19, 2012·Mediators of Inflammation·Jan VítečekLukáš Kubala
Apr 27, 2012·PloS One·Carmen María Fernández-MartosFrancisco Javier Rodriguez
Aug 13, 2015·Neurochemistry International·Ayodeji A AsuniMartin J Sadowski
Nov 27, 2015·Nature Communications·Liqun WangMel B Feany
Jan 9, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Magali DumontM Flint Beal
Feb 28, 2021·Acta Biochimica Et Biophysica Sinica·Yinhua NiZhengwei Fu