NADPH oxidase contributes to streptozotocin-induced neurodegeneration.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory. The neurodegeneration induced by AD has been linked to oxidative damage. However, little is known about the involvement of NADPH oxidase 2 (Nox2), a multisubunit enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the pathogenesis of AD. The main purpose of this study was to investigate the involvement of Nox2 in memory, in AD-related brain abnormalities, oxidative damage, inflammation and neuronal death in the hippocampus in the streptozotocin (STZ)-induced AD-like state by comparing the effects of that drug on mice lacking gp91phox-/- and wild-type (Wt) mice. Nox2 gene expression was found increased in Wt mice after STZ injection. In object recognition test, Wt mice injected with STZ presented impairment in short- and long-term memory, which was not observed following Nox2 deletion. STZ treatment induced increased phosphorylation of Tau and increased amyloid-β, apoptosis-inducing factor (AIF) and astrocyte and microglial markers expression in Wt mice but not in gp91phox-/-. STZ treatment increased oxidative damage and pro-inflammatory cytokines' release in Wt mice, which was not observed in gp91phox-/- mice. Nox2 deletion had a positive effect on the IL-10 baseline production, suggesting that this cytokine might contribute to the neuroprotection mechanism against STZ-induced neurodegeneration. In summary, our data suggest that the Nox2-dependent reactive oxygen species (ROS) generation contributes to the STZ-induced AD-like state.

• Authors: Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Andrea Rodrigues Vasconcelos, Cristoforo Scavone, Rosana Camarini, Marina S Hernandes, Luiz Roberto Britto
• Journal: Neuroscience (Neuroscience) Vol. 358 Pg. 227-237 (09 01 2017) ISSN: 1873-7544 [Electronic] United States
• PMID: 28687315 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Aldehydes
• Amyloid beta-Peptides
• Antibiotics, Antineoplastic
• Apoptosis Inducing Factor
• CD11b Antigen
• Cytokines
• Glial Fibrillary Acidic Protein
• Pirb protein, mouse
• RNA, Messenger
• Receptors, Immunologic
• tau Proteins
• Streptozocin
• NADPH Oxidase 2
• 4-hydroxy-2-nonenal

Topics

• Aldehydes (metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Antibiotics, Antineoplastic (toxicity)
• Apoptosis Inducing Factor (metabolism)
• CD11b Antigen (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Glial Fibrillary Acidic Protein (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NADPH Oxidase 2 (genetics, metabolism)
• Neurodegenerative Diseases (chemically induced)
• RNA, Messenger (metabolism)
• Receptors, Immunologic (deficiency, genetics)
• Recognition, Psychology (physiology)
• Streptozocin (toxicity)
• tau Proteins (metabolism)