Striatal Protection in nNOS Knock-Out Mice After Quinolinic Acid-Induced Oxidative Damage

Dec 8, 2018Neurochemical research

Protection of Movement Control Area in Mice Without nNOS After Chemical-Induced Oxidative Damage

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Abstract

The absence of neuronal nitric oxide synthase (nNOS) in mice provides protection against oxidative damage induced by quinolinic acid, leading to decreased circling behavior and oxidative stress.

Neuronal nitric oxide synthase (nNOS) has been implicated in oxidative cellular damage under pathological conditions.
Activation of NMDA receptors by quinolinic acid (QUIN) increases nNOS function, which is associated with heightened oxidative stress.
In nNOS knock-out mice, QUIN-induced oxidative damage in the striatum is reduced compared to wild-type and heterozygote mice.
Decreased circling behavior and oxidative stress were observed in the absence of nNOS during QUIN exposure.
GABA depletion was partially protected in nNOS knock-out mice, indicating a role for nNOS-derived nitric oxide in neurological damage.

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Under pathological conditions, nitric oxide can become a mediator of oxidative cellular damage, generating an unbalance between oxidant and antioxidant systems. The participation of neuronal nitric oxide synthase (nNOS) in the neurodegeneration mechanism has been reported; the activation of N-methyl-D-aspartate (NMDA) receptors by agonist quinolinic acid (QUIN) triggers an increase in nNOS function and promotes oxidative stress. The aim of the present work was to elucidate the participation of nNOS in QUIN-induced oxidative stress in knock-out mice (nNOS-/-). To do so, we microinjected saline solution or QUIN in the striatum of wild-type (nNOS +/+), heterozygote (nNOS+/-), and knock-out (nNOS-/-) mice, and measured circling behavior, GABA content levels, oxidative stress, and NOS expression and activity. We found that the absence of nNOS provides a protection against striatal oxidative damage induced by QUIN, resulting in decreased circling behavior, oxidative stress, and a partial protection reflected in GABA depletion. We have shown that nNOS-derived NO is involved in neurological damage induced by oxidative stress in a QUIN-excitotoxic model.

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