Van Damme Philip, Leyssen Maarten, Callewaert Geert, Robberecht Wim, Van Den Bosch Ludo
Laboratory for Neurobiology, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Neurosci Lett. 2003 Jun 5;343(2):81-4. doi: 10.1016/s0304-3940(03)00314-8.
alpha-Amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated excitotoxicity has been implicated in the selective motor neuron loss in amyotrophic lateral sclerosis (ALS). The extent to which excitotoxicity contributes to motor neuron death remains incompletely understood. We therefore tested the potent and selective AMPA/kainate receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) on motor neurons in culture and in the G93A mouse model for familial ALS. Kainate-induced currents and changes in intracellular Ca(2+) concentration were measured with the perforated patch clamp technique combined with Ca(2+) imaging, motor neuron death was quantified by counting experiments and G93A mice were treated with saline or 8 mg/kg NBQX. NBQX blocked kainate-induced currents and concomitant changes in intracellular Ca(2+), prevented the kainate-induced motor neuron death, and prolonged survival of G93A mice.
α-氨基-3-羟基-5-甲基异恶唑丙酸（AMPA）受体介导的兴奋毒性与肌萎缩侧索硬化症（ALS）中运动神经元的选择性丧失有关。兴奋毒性对运动神经元死亡的影响程度仍未完全了解。因此，我们在培养的运动神经元以及家族性ALS的G93A小鼠模型中测试了强效且选择性的AMPA/海人藻酸受体拮抗剂1,2,3,4-四氢-6-硝基-2,3-二氧代-苯并[f]喹喔啉-7-磺酰胺（NBQX）。采用穿孔膜片钳技术结合Ca²⁺成像测量海人藻酸诱导的电流和细胞内Ca²⁺浓度的变化，通过计数实验对运动神经元死亡进行定量，并用生理盐水或8mg/kg NBQX处理G93A小鼠。NBQX阻断了海人藻酸诱导的电流以及细胞内Ca²⁺的相应变化，防止了海人藻酸诱导的运动神经元死亡，并延长了G93A小鼠的存活时间。
