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

VIVIANE GLASER; VALERIA P CARLINI; LAURA GABACH,; MARISA GHERSI,; SUSANA R BARIOGLIO, ; OSCAR A RAMIREZ; ALEXANDRA LATINI; MARIELA PEREZ

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Año: 2010 vol. 30 p. 1067 - 1075

0272-4340

Leucine (LEU) accumulates in fluids and tissues of patients affected by maple syrup urine disease (MSUD), 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 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 the step-down test in rats. In addition, the LEU effects on the electrophysiological parameter, long-term potentiation (LTP) generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats were bilaterally administrated with LEU (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. LEU-treated animals showed impairment in memory consolidation and a complete impairment of 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.ex-vivo biochemical measurements. LEU-treated animals showed impairment in memory consolidation and a complete impairment of 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.