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Metab Brain Dis ; 27(4): 479-86, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22699997

RESUMEN

Hyperornithinemia is the biochemical hallmark of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, an inherited metabolic disease clinically characterized by mental retardation whose pathogenesis is still poorly known. In the present work, we produced a chemical animal model of hyperornithinemia induced by a subcutaneous injection of saline-buffered Orn (2-5 µmol/g body weight) to rats. High brain Orn concentrations were achieved, indicating that Orn is permeable to the blood brain barrier. We then investigated the effect of early chronic postnatal administration of Orn on physical development and on the performance of adult rats in the open field, the Morris water maze and in the step down inhibitory avoidance tasks. Chronic Orn treatment had no effect on the appearance of coat, eye opening or upper incisor eruption, nor on the free-fall righting reflex and on the adult rat performance in the Morris water maze and in the inhibitory avoidance tasks, suggesting that physical development, aversive and spatial localization were not changed by Orn. However, Orn-treated rats did not habituate to the open field apparatus, implying a deficit of learning/memory. Motor activity was the same for Orn- and saline- injected animals. We also verified that Orn subcutaneous injections provoked lipid peroxidation in the brain, as determined by a significant increase of thiobarbituric acid-reactive substances levels. Our results indicate that chronic early postnatal hyperornithinemia may impair the central nervous system, causing minor disabilities which result in specific learning deficiencies.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/inducido químicamente , Discapacidades para el Aprendizaje/inducido químicamente , Discapacidades para el Aprendizaje/psicología , Ornitina/toxicidad , Errores Innatos del Metabolismo de los Aminoácidos/psicología , Amoníaco/sangre , Animales , Animales Recién Nacidos , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Citrulina/análogos & derivados , Citrulina/sangre , Cognición/efectos de los fármacos , Cognición/fisiología , Discapacidades del Desarrollo/inducido químicamente , Modelos Animales de Enfermedad , Semivida , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Ornitina/farmacocinética , Equilibrio Postural/efectos de los fármacos , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
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