Brain nitric oxide synthases and mitochondrial function.
Nitric oxide is a small signaling molecule, which may act as a neurotransmitter and neuromodulator, exerting a regulatory effect on neuronal function. It can diffuse from its site of synthesis to different intra and extracellular compartments, being therefore present in the pre-synaptic, synaptic and post-synaptic spaces. Recently, a NOS located in the mitochondria (mtNOS) has been observed in different brain regions, responsible for the production of NO in these organelles and identified as nNOS. A regulatory effect of NO on mitochondrial function was described in brain mitochondria, where NO acts mainly by inhibiting cytochrome oxidase activity. Hippocampal mitochondrial dysfunction and decreased mtNOS activity and expression were reported in association with ultrastructural damage in an experimental model of hepatic encephalopathy. Enriched environment exposure preserved the aged animals from spatial cognition impairment; also environment and training modulated neuronal plasticity in pre-pubertal rats through NO-dependent mechanisms. In addition, brain cortical mitochondrial respiration and mtNOS activity and expression were analyzed as function of age. Mitochondrial NO production showed a decreasing tendency as a function of age. These results are in accordance with the protein expression analyzed by Western Blot of mitochondrial fractions which was 6.5 times higher in 1 month aged rats as compared with 14 old animals. Concomitant with these results, a clear increasing oxygen uptake tendency in state 3 respiration was observed, meanwhile only a slight increase was observed in state 4. All these results seems to be clearly related with the reversible and concentration-dependent attenuation of the respiratory chain by NO.
Bustamante
Juanita
J
Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. juanitab@ffyb.uba.ar
Czerniczyniec
Analía
A
Lores-Arnaiz
Silvia
S
D000375:Aging; D000818:Animals; D001921:Brain / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D051381:Rats
D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I