title: Apocynin administration does not improve behavioral and neuropathological deficits in a transgenic mouse model of Alzheimer's disease.
abstract: In addition to mitochondria, NADPH oxidase (NOX) is a source of oxidative stress, which can induce oxidative damage in Alzheimer's disease (AD). For this reason, several groups have investigated the effect of its inhibition. In AD mice, NADPH oxidase 2 (NOX2) deficiency improved behavior and cerebrovascular function, and reduced oxidative stress. In our study, we administered the NOX inhibitor apocynin to Tg19959 mice, and found that it did not improve cognitive and synaptic deficits, and did not decrease amyloid deposition, microgliosis and hyperphosphorylated tau. However, apocynin reduced carbonyl levels in the cerebral cortex but not the hippocampus, which may have not been sufficient to ameliorate symptoms. Also, the reduction of NOX-mediated oxidative stress may not be sufficient to prevent AD, since other sources of reactive oxygen species such as mitochondria may be more important.
authors.affiliation: Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 East 68th Street, New York, NY 10065, USA. mad2138@med.cornell.edu
authors.forename: Magali
authors.initials: M
authors.lastname: Dumont
authors.forename: Cliona
authors.initials: C
authors.lastname: Stack
authors.forename: Ceyhan
authors.initials: C
authors.lastname: Elipenhali
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wille
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C056165:acetovanillone