The intra-hippocampal leucine administration impairs memory consolidation and LTP

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

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 maplesyrup urine disease (MSUD), an inherited metabolic disorder, predominantlycharacterized by neurological dysfunction. Although, a variable degree ofcognition/psychomotor delay/mental retardation is found in a considerable number ofMSUD individuals, the mechanisms underlying the neuropathology of these alterationsare still not defined. Therefore, the aim of this study was to investigate the effect ofacute 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. MaleWistar rats were bilaterally administrated with LEU (80 nmol/hippocampus; 160nmol/rat) or artificial cerebrospinal fluid (controls) into the hippocampus immediatelypost-training in the behavioral task. Twenty-four hours after training in the step-downtest, the latency time was evaluated and afterwards animals were sacrificed for assessingthe ex-vivo biochemical measurements. LEU-treated animals showed impairment inmemory consolidation and a complete impairment of LTP generation at supramaximalstimulation. In addition, a significant increment in complex IV activity was observed inhippocampus from LEU administered rats. These data strongly indicates that LEUcompromise memory consolidation, and that impairment of LTP generation andunbalance of the respiratory chain may be plausible mechanisms underlying thedeleterious LEU effect on cognition.