Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: reversal by NMDA receptor blockade

Brain Research Bulletin
S O'MahonyB E Leonard

Abstract

Ample experimental evidence indicates that acute beta-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex. In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA) receptors, was proposed as a pivotal mechanism in beta-amyloid-induced neurodegeneration. A definite measure of NMDA receptor-mediated processes and subsequent Ca2+ entry is the induction of Ca2+/calmodulin-activated neuronal nitric oxide synthase (nNOS) in nerve cells. In the present account we therefore assessed activation of nNOS in correlation with cholinergic decline after beta-amyloid(1-42) or beta-amyloid(25-35) infusion into the rat nucleus basalis. The results demonstrate the beta-amyloid conformation-dependent enhancement of cortical nitric oxide synthase (NOS) activity. Furthermore, chronic application of the polyamine site NMDA receptor blocker ifenprodil effectively attenuated beta-amyloid neurotoxicity. We propose that nNOS activation reflects the degree of beta-amyloid-induced excitotoxic injury in a proportional manner. Moreover, Ca2+-mediated processes via NMDA receptors, or direct binding of beta-amyloid to this re...Continue Reading

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Citations

Aug 11, 2004·Behavioural Brain Research·Tamás SzabadosRudolf Urbanics
Jan 6, 2000·Progress in Neuro-psychopharmacology & Biological Psychiatry·T HarkanyC Nyakas
Mar 15, 2000·Brain Research Bulletin·E Sotirov, M Papasova
Sep 3, 2011·Behavioural Brain Research·Caroline ChambonWojciech Danysz
Sep 2, 2010·Nitric Oxide : Biology and Chemistry·Anna V GoryachevaEugenia B Manukhina
Jan 22, 2008·Neurochemistry International·Mikhail Yu StepanichevNatalia V Gulyaeva
Feb 1, 2005·Brain Research Bulletin·Maria Luiza Nunes Mamede RosaElaine Aparecida Del Bel
Feb 19, 2005·Neurobiology of Aging·Elisa Mitiko KawamotoTania Marcourakis
Apr 15, 2015·The Journal of Nutritional Biochemistry·Anand Kamal Sachdeva, Kanwaljit Chopra
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Dec 13, 2002·Journal of Neuroscience Research·Mikhail Yu StepanichevNatalia V Gulyaeva
Dec 16, 2006·Journal of Neuroscience Research·Julio Santos-TorresJavier Yajeya
Jul 9, 2002·Journal of Basic and Clinical Physiology and Pharmacology·Przemyslaw MikolajczakTeresa Bobkiewicz-Kozlowska
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Jan 15, 2020·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Jul 22, 2005·Neuroscience and Behavioral Physiology·M Yu StepanichevN V Gulyaeva

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