Basal ganglia neuroprotection with anticonvulsants after energy stress: a comparative study.
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.
UMRS INSERM U 930, CNRS ERL 3106, Imagerie et cerveau, Tours 37000, France.
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S
Arpin
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Lagrue
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Bodard
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Chalon
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P
Castelnau
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects*; D001480:Basal Ganglia Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D000077213:Lamotrigine; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000473:pathology; D018696:Neuroprotective Agents; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D050483:Dopamine Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D014227:Triazines; D000077213:Lamotrigine