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The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility

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Abstract

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in hepatic cytosolic aminotransferase. Affected patients usually present a variable degree of mental retardation, which may be related to the level of plasma tyrosine. In the present study we evaluated effect of chronic administration of L-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase and complexes I, II, II-III and IV in cerebral cortex, hippocampus and striatum of rats in development. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); rats were killed 12 h after last injection. Our results demonstrated that L-tyrosine inhibited the activity of citrate synthase in the hippocampus and striatum, malate dehydrogenase activity was increased in striatum and succinate dehydrogenase, complexes I and II-III activities were inhibited in striatum. However, complex IV activity was increased in hippocampus and inhibited in striatum. By these findings, we suggest that repeated administrations of L-tyrosine cause alterations in energy metabolism, which may be similar to the acute administration in brain of infant rats. Taking together the present findings and evidence from the literature, we hypothesize that energy metabolism impairment could be considered an important pathophysiological mechanism underlying the brain damage observed in patients with tyrosinemia type II.

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Acknowledgments

This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde—Universidade do Extremo Sul Catarinense (UNESC), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Correspondence to Emilio L. Streck.

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Ferreira, G.K., Carvalho-Silva, M., Gomes, L.M. et al. The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility. Metab Brain Dis 30, 215–221 (2015). https://doi.org/10.1007/s11011-014-9615-3

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