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Induction of NOS and nitrotyrosine expression in the rat striatum following experimental hepatic encephalopathy

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Abstract

Hepatic encephalopathy (HE) is a neurologic disease associated with hepatic dysfunction. Astroglial and neuronal alterations have been described in the basal ganglia in HE. Our study was performed to determine whether such alterations are mediated by nitric oxide (NO), by using an experimental model of HE (portacaval anastomosis [PCA]). The expression of the NO synthases (nNOS and iNOS) and the production of nitrotyrosine (NT) were evaluated in the striatum of rats exposed to PCA for 1 and 6 months. The expression of nNOS in the striatal neurons of PCA rats was increased compared to controls. nNOS expression was also detectable in astrocytes after 6 months of exposure to PCA. Whereas astroglial cells in the normal striatum showed no iNOS expression, iNOS was expressed in the astrocytes of PCA brains, mainly in perivascular processes at 6 months PCA exposure (demonstrated by colocalization with GFAP). The increased expression of both the nNOS and iNOS isoforms in PCA rats might indicate a critical role for NO in the pathomechanism of HE. To study the potential cell damage caused by NO, the deposition of NT in PCA-rats was analysed. Nitrotyrosine was detected in neurons although it was mainly seen in the astrocytes of PCA brains, in which double immunolabelling showed NT to be colocalized with GFAP. Thus, the present study shows the induction of iNOS and NT in astrocytes, which increases with the duration of PCA exposure. This suggests that the induced astroglial production of NO during PCA might be one of the main factors contributing to HE.

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Acknowledgements

We are grateful to Adrian Burton for reviewing the English version of the manuscript. This work was partially supported by a grant from the Spanish Ministry of Health (G03/155).

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  1. Departamento de Biología Celular y Genética, Facultad de Biología, Universidad de Alcalá, 28871, Madrid, Spain

    Isabel Suárez, Guillermo Bodega & Miguel Rubio

  2. Departamento de Biología Celular, Universidad Complutense, 28040, Madrid, Spain

    Benjamín Fernández

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  1. Isabel Suárez
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  2. Guillermo Bodega
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  4. Benjamín Fernández
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Correspondence to Isabel Suárez.

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Suárez, I., Bodega, G., Rubio, M. et al. Induction of NOS and nitrotyrosine expression in the rat striatum following experimental hepatic encephalopathy. Metab Brain Dis 24, 395–408 (2009). https://doi.org/10.1007/s11011-009-9154-5

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