Basal ganglia neuroprotection with anticonvulsants after energy stress: a comparative study
- 103 Downloads
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model provides a valuable paradigm of the energy deficiency disorders found in childhood. In such disorders, anticonvulsants may provide neuroprotection by modulating cellular energy consumption and by exerting favorable pleiotropic effects on neuronal survival. To verify such hypothesis, we tested the effects of levetiracetam, vigabatrin, gabapentine, pregabaline, tiagabine, clonazepam and lamotrigine on neuroprotection in the MPTP mouse model. The membrane dopamine transporter (DAT) density, which provides a reliable index of dopaminergic neurons survival in the basal ganglia, was assessed by semi-quantitative autoradiography of the striatum. Unlike all other anticonvulsants tested, lamotrigine provided a significant and dose-dependent neuroprotection in these experimental conditions. Lamotrigine, a widely used and well-tolerated molecule in children, could provide neuroprotection in various energy deficiency disorders.
KeywordsBasal ganglia Mitochondria MPTP Leigh syndrome Neuroprotection Anticonvulsant
The authors thank M.-C. Furon for technical assistance with animal handling, L. Garreau, M-P. Vilar, and J. Vergotte for contributive support on experiments, and C. Hoinard for expert contribution to statistical analysis. The authors also thank F. Paillard for editing the manuscript. This work was supported by fellowships from the Fondation pour la Recherche Medicale (FRM) and from the DRASS Region Centre, France, to S. Arpin.
- Chalon S, Garreau L, Emond P, Zimmer L, Vilar MP, Besnard JC, Guilloteau D (1999) Pharmacological characterization of (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4′-methylphenyl)n ortropane as a selective and potent inhibitor of the neuronal dopamine transporter. J Pharmacol Exp Ther 291:648–654PubMedGoogle Scholar
- Costa C, Belcastro V, Tozzi A, Di Filippo M, Tantucci M, Siliquini S, Autuori A, Picconi B, Spillantini MG, Fedele E, Pittaluga A, Raiteri M, Calabresi P (2008) Electrophysiology and pharmacology of striatal neuronal dysfunction induced by mitochondrial complex I inhibition. J Neurosci 28:8040–8052CrossRefPubMedGoogle Scholar
- Palma E, Ragozzino D, Di Angelantonio S, Mascia A, Maiolino F, Manfredi M, Cantore G, Esposito V, Di Gennaro G, Quarato P, Miledi R, Eusebi F (2007) The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA receptors upon repetitive activation. Epilepsia 48:1842–1849CrossRefPubMedGoogle Scholar
- Saudubray J-M, Charpentier C (1995) Clinical phenotypes: diagnosis/algoritms. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. Mc Graw-Hill, New York, pp 327–400Google Scholar