title: Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons.
abstract: L-valine is a branched-chain amino acid (BCAA) largely used as dietary integrator by athletes and involved in some inherited rare diseases such as maple syrup urine disease. This pathology is caused by an altered BCAA metabolism with the accumulation of toxic keto acids in tissues and body fluids with consequent severe neurological symptoms. In animal models of BCAA accumulation, increased oxidative stress levels and lipid peroxidation have been reported. The aim of this study was to analyze both whether high BCAA concentrations in neurons induce reactive oxygen species (ROS) production and whether, by performing electrophysiological recordings, the neuronal functional properties are modified. Our results demonstrate that in primary cortical cultures, a high dose of valine increases ROS production and provokes neuronal hyperexcitability because the action potential frequencies and the persistent sodium current amplitudes increase significantly compared to non-treated neurons. Since Baicalein, a flavone obtained from the Scutellaria root, has been shown to act as a strong antioxidant with neuroprotective effects, we evaluated its possible antioxidant activity in primary cortical neurons chronically exposed to L-valine. The preincubation of cortical neurons with Baicalein prevents the ROS production and is able to revert both the neuronal hyperexcitability and the increase of the persistent sodium current, indicating a direct correlation between the ROS production and the altered physiological parameters. In conclusion, our data show that the electrophysiological alterations of cortical neurons elicited by high valine concentration are due to the increase in ROS production, suggesting much caution in the intake of BCAA dietary integrators.
authors.affiliation: IRCCS S. Lucia Foundation, Via del Fosso di Fiorano, 64, Rome 00143, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Caioli
authors.affiliation: Department of Sciences, University Roma Tre, Viale G. Marconi, 446, Rome 00146, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Candelotti
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 1,Rome 00133, Italy.
authors.forename: Jens Z
authors.initials: JZ
authors.lastname: Pedersen
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, Rome 00133, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Saba
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, Rome 00133, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Antonini
authors.affiliation: Department of Sciences, University Roma Tre, Viale G. Marconi, 446, Rome 00146, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Incerpi
authors.affiliation: IRCCS S. Lucia Foundation, Via del Fosso di Fiorano, 64, Rome 00143, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, Rome 00133, Italy. Electronic address: zona@uniroma2.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D014633:Valine / Q000494:pharmacology*
chemical_list: D044950:Flavanones; D017382:Reactive Oxygen Species; C006680:baicalein; D012964:Sodium; D014633:Valine
keywords: Antioxidant; Baicalein; Branched-chain amino acids; Neuronal hyperexcitability; Persistent sodium current; Reactive oxygen species