Memantine protects against secondary neuronal degeneration in lateral geniculate nucleus and superior colliculus after retinal damage in mice
Memantine protects against secondary neuronal degeneration in lateral geniculate nucleus and superior colliculus after retinal damage in mice
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DOI：
10.1111/j.1755-5949.2008.00050.x
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发表时间：
2008-01-01
影响因子：
5.5
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Ito, Yasushi;Nakamura, Shinsuke;Hara, Hideaki
本研究的目的是在小鼠上确定美金刚，一种N-甲基-D-天冬氨酸（NMDA）亚型的谷氨酸受体拮抗剂，玻璃体内注射NMDA诱导视网膜损伤后，可防止背外侧膝状体核（dLGN）和上级丘（SC）的神经元变性。（20 mM/2 μ l）注射到小鼠左眼的玻璃体中（第0天）。为了评价美金刚的神经保护作用，将小鼠分配到两个美金刚处理组之一：每天接受30 mg/kg/天的美金刚，p.o.预处理组在玻璃体内注射NMDA前1 h给药至第90天（预处理组）或第7天至第90天（后处理组），对玻璃体内注射NMDA引起的视网膜损伤有明显的抑制作用，对侧dLGN和SC的跨突触神经元变性也有明显的抑制作用。尽管后处理组的小鼠没有显示出这种视网膜损伤的逆转，但它们确实表现出对对侧LGN和SC中神经元变性的保护。这些数据表明，即使在视网膜神经节细胞（RGC）死亡后开始治疗，美金刚也可以预防小鼠大脑（LGN和SC）的跨突触神经元变性。美金刚可以预防视觉通路中大脑区域的继发性神经元变性小鼠视网膜损伤后发生的变性。
The purpose of this study, on mice, was to determine whether memantine, a glutamate-receptor antagonist of the N-methyl-D-aspartate (NMDA) subtype, protects against neuronal degeneration in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) after the induction of retinal damage by intravitreal injection of NMDA.NMDA (20 mM/2 mu l) was injected into the vitreous body of the left eye in mice (day 0). To evaluate the neuroprotective effect of memantine, mice were assigned to one of two memantine-treated groups: receiving a daily administration of memantine at 30 mg/kg/day, p.o. either from day 0 (administered at 1 h before NMDA injection) to day 90 (pretreated group) or from day 7 to day 90 (post-treated group).The pretreated group exhibited significant suppression of the retinal damage induced by intravitreal injection of NMDA and significant prevention of transsynaptic neuronal degeneration in the dLGN and SC on the contralateral side. Although the mice of the post-treated group displayed no reversion of such retinal damage, they did exhibit protection against neuronal degeneration in the LGN and SC on the contralateral side. These data indicate that memantine can protect against transsynaptic neuronal degeneration in the murine brain (LGN and SC) even if treatment is begun after retinal ganglion cell (RGC) death has started.Memantine protects against the secondary neuronal degeneration in brain regions in the visual pathway that occurs after retinal damage in mice.