Arpin S, Lagrue E, Bodard S, Chalon S, Castelnau P
UMRS INSERM U 930, CNRS ERL 3106, Imagerie et cerveau, Tours 37000, France.
Metab Brain Dis. 2009 Sep;24(3):453-61. doi: 10.1007/s11011-009-9144-7.
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.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠模型为儿童期发现的能量缺乏性疾病提供了一个有价值的范例。在这类疾病中，抗惊厥药可能通过调节细胞能量消耗以及对神经元存活发挥有利的多效性作用来提供神经保护。为验证这一假设，我们在MPTP小鼠模型中测试了左乙拉西坦、氨己烯酸、加巴喷丁、普瑞巴林、噻加宾、氯硝西泮和拉莫三嗪对神经保护的作用。通过纹状体的半定量放射自显影评估膜多巴胺转运体（DAT）密度，该密度是基底节中多巴胺能神经元存活的可靠指标。与所有其他测试的抗惊厥药不同，在这些实验条件下，拉莫三嗪提供了显著的剂量依赖性神经保护作用。拉莫三嗪是一种在儿童中广泛使用且耐受性良好的分子，可在各种能量缺乏性疾病中提供神经保护。
