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 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.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.

Venerosi, A., Martire, A., Rungi, A., Pieri, M., Ferrante, A., Zona, C., et al. (2011). Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis [10.1002/mnfr.201000296].

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

PIERI, MASSIMO;ZONA, CRISTINA;
2011-01-05

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 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.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.
5-gen-2011
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
English
Con Impact Factor ISI
Venerosi, A., Martire, A., Rungi, A., Pieri, M., Ferrante, A., Zona, C., et al. (2011). Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis [10.1002/mnfr.201000296].
Venerosi, A; Martire, A; Rungi, A; Pieri, M; Ferrante, A; Zona, C; Popoli, P; Calamandrei, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/16197
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