Selective protection against oxidative damage in brain of mice with a targeted disruption of the neuronal nitric oxide synthase gene.
Nitric oxide (NO) is an essential messenger molecule in brain, where it is produced in neurons mostly by the activity of the neuronal isoform of nitric oxide synthase (nNOS). To understand the participation of the different isoforms of NOS in physiological functioning and in pathological processes, mice with null mutations for each of the NOS isoforms have been generated. In the present paper, we report that there is a selective protection from oxidative damage in the brain of mice with a targeted disruption of the nNOS gene. The cerebellum of these mice shows reduced levels of lipid peroxidation (LP) at the different ages tested, compared with wild-type mice, and also a reduction in the formation of reactive oxygen species (ROS). We observed a decrease of LP in cortex, and no effect on either LP or ROS formation was observed in striatum of knockout mice compared with wild type. We also report increased spontaneous motor activity of knockout mice. The expression and activity of nNOS are crucial to maintain redox status in brain, and we consider that the alteration in oxidative damage may help us to explain the phenotypical characteristics of nNOS knockout mice and their differential susceptibility to brain insults.
Martínez-Lazcano
Juan Carlos
JC
Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, D.F.
Pérez-Severiano
Francisca
F
Escalante
Bruno
B
Ramírez-Emiliano
Joel
J
Vergara
Paula
P
González
Rosa O
RO
Segovia
José
J
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002531:Cerebellum / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D016009:Chi-Square Distribution; D007527:Isoenzymes; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D007527:Isoenzymes; D017382:Reactive Oxygen Species; D052248:Nitric Oxide Synthase Type I