The intra-hippocampal leucine administration impairs memory consolidation and LTP generation in rats

GLASER VIVIANE; GRECI EIDT; MARÍLIA OLIVEIRA BÙRIGO; VALERIA PAOLA CARLINI; GABACH LAURA; GHERSI MARISA; SUSANA RUBIALES DE BARIOGLIO; OSCAR RAMIREZ; PERÉZ MF; ALEXANDRA LATINI

Foz do Iguazù

Congreso; XL Annual Meeting of The Brazilian Biochemistry and Molecular Biology Society; 2011

Biochemistry and Molecular Biology Society

Leucine (LEU) accumulates in fluids and tissues of patients affected by maple syrup urine disease (MSUD), an inherited metabolic disorder, characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of MSUD individuals, 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 LEU administration in rats on the long-term potentiation (LTP) generation, in the step-down behavioral test and on the activities of the respiratory chain.Male Wistar rats were bilaterally administrated with LEU (80nmol/hippocampus;160nmol/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. LEU-treated animals showed impairment in memory consolidation and LTP generation at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from LEU administered rats. These data strongly indicates that LEU compromise memory consolidation, and that impairment of LTP generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious LEU effect on cognition.