title: Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis.
abstract: METHODS
  We hypothesized that chronic supplementation with branched chain amino acids (BCAAs) affects neurobehavioral development in vulnerable gene backgrounds.
  
  
  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 16 wk 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Aldina
authors.initials: A
authors.lastname: Venerosi
authors.forename: Alberto
authors.initials: A
authors.lastname: Martire
authors.forename: Angela
authors.initials: A
authors.lastname: Rungi
authors.forename: Massimo
authors.initials: M
authors.lastname: Pieri
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferrante
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
authors.forename: Patrizia
authors.initials: P
authors.lastname: Popoli
authors.forename: Gemma
authors.initials: G
authors.lastname: Calamandrei
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000009:adverse effects*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D019587:Dietary Supplements / Q000009:adverse effects; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity; D006948:Hyperkinesis / Q000209:etiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017288:Pain Threshold; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012720:Severity of Illness Index; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D000597:Amino Acids, Branched-Chain; D051272:Glucose Transporter Type 1; D009419:Nerve Tissue Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C495678:Slc2a1 protein, mouse; D018698:Glutamic Acid