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The Intra-Hippocampal Leucine Administration Impairs Memory Consolidation and LTP Generation in Rats

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Abstract

Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder, predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of individuals affected by this deficieny, the mechanisms underlying the neuropathology of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter, long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls) into the hippocampus immediately post-training in the behavioral task. Twenty-four hours after training in the step-down test, the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements. Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from leucine-administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious leucine effect on cognition.

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Acknowledgments

This study was supported by grants from CONICET (Consejo Nacional de Investigación Científica y Técnica), SECyT (Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba), and by grants from FAPESC (Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Latini A is a CNPq fellow.

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Authors and Affiliations

  1. Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário—Trindade, Florianópolis, SC, CEP 88040-900, Brazil

    Viviane Glaser & Alexandra Latini

  2. Departamento de Farmacologia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, IFEC-CONICET, Córdoba, Argentina

    Laura Gabach, Marisa Ghersi, Susana Rubiales de Barioglio, Oscar A. Ramirez & Mariela F. Perez

  3. Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

    Valeria P. Carlini

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  1. Viviane Glaser
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  2. Valeria P. Carlini
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  3. Laura Gabach
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  4. Marisa Ghersi
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  7. Mariela F. Perez
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  8. Alexandra Latini
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Correspondence to Alexandra Latini.

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Viviane Glaser, Valeria P. Carlini, Mariela F. Perez, Alexandra Latini contributed equally to this study, Viviane Glaser, Valeria P. Carlini should be considered as joint first authors and Mariela F. Perez, Alexandra Latini should be considered as joint last corresponding authors.

Valeria P. Carlini, Rubiales de Barioglio, Oscar A. Ramirez, Mariela F. Perez, and Alexandra Latini are established investigators from CONICET or CNPq.

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Glaser, V., Carlini, V.P., Gabach, L. et al. The Intra-Hippocampal Leucine Administration Impairs Memory Consolidation and LTP Generation in Rats. Cell Mol Neurobiol 30, 1067–1075 (2010). https://doi.org/10.1007/s10571-010-9538-4

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