Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis

Aldina Venerosi, Alberto Martire, Angela Rungi, Massimo Pieri, Antonella Ferrante, Cristina Zona, Patrizia Popoli, Gemma Calamandrei

Research output: Contribution to journalArticlepeer-review

Abstract

Scope: We hypothesized that chronic supplementation with branched chain amino acids (BCAAs) affects neurobehavioral development in vulnerable gene backgrounds. Methods and results: A murine model of amyotrophic lateral sclerosis (ALS), G93A mice bearing the mutated human superoxide dismutase 1 (SOD1) gene, and control mice received from 4 to 16wk of age dietary supplementation with BCAAs at doses comparable to human usage. Motor coordination, exploratory behaviors, pain threshold, synaptic activity and response to glutamatergic stimulation in primary motor cortex slices were evaluated between the 8th and 16th week. The glial glutamate transporter 1 (GLT-1) and metabotropic glutamate 5 receptor (mGlu5R) were analyzed by immunoblotting in cortex, hippocampus and striatum. BCAAs induced hyperactivity, decreased pain threshold in wild-type mice and exacerbated the motor deficits of G93A mice while counteracting their abnormal pain response. Electrophysiology on G93A brain slices showed impaired synaptic function, reduced toxicity of GLT-1 blocking and increased glutamate toxicity prevented by BCAAs. Immunoblotting indicated down-regulation of GLT-1 and mGlu5R in G93A, both effects counteracted by BCAAs. Conclusion: These results, though not fully confirming a role of BCAAs in ALS-like etiology in the genetic model, clearly indicate that BCAAs' complex effects on central nervous system depend on gene background and raise alert over their spread use.

Original languageEnglish
Pages (from-to)541-552
Number of pages12
JournalMolecular Nutrition and Food Research
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Amyotrophic lateral sclerosis
  • Branched chain amino acids
  • Central nervous system
  • Excitotoxicity
  • Transgenic mice

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

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