Rapastinel alleviates the neurotoxic effect induced by NMDA receptor blockade in the early postnatal mouse brain
Rapastinel alleviates the neurotoxic effect induced by NMDA receptor blockade in the early postnatal mouse brain
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DOI：
10.1007/s00406-020-01180-5
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发表时间：
2020-08
影响因子：
4.7
通讯作者：
A. Vasilescu;A. Mallien;N. Pfeiffer;U. Lang;P. Gass;D. Inta
中科院分区：
文献类型：
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作者：
A. Vasilescu;A. Mallien;N. Pfeiffer;U. Lang;P. Gass;D. Inta
Rapastinel是一种新型精神活性物质，作为N-甲基-D-天冬氨酸受体（NMDAR）激动剂，在动物模型中触发抗抑郁和抗精神病样作用。然而，目前尚不清楚雷帕替奈是否具有比快速起效的多巴胺能抗抑郁药（如氯胺酮）更好的副作用，氯胺酮会引发围产期啮齿动物皮质的神经毒性和长期的精神分裂症样改变。在这里，我们发现了一个显着的神经保护作用雷帕替奈对NMDAR拮抗剂MK-801诱导的细胞凋亡引起的氯氮平和mGlu 2/3激动剂LY354740相比。这些结果表明雷帕替奈在改善神经发育期间由NMDAR阻断诱导的有害作用方面的潜在治疗/预防作用。
Rapastinel is a novel psychoactive substance that acts as an N-methyl-D-aspartate-receptor (NMDAR) agonist and triggers antidepressant- and antipsychotic-like effects in animal models. However, it is unknown if rapastinel possesses a better side-effect profile than fast-acting glutamatergic antidepressants, like ketamine, which trigger neurotoxicity in the perinatal rodent cortex and protracted schizophrenia-like alterations. Here we found a remarkable neuroprotective effect of rapastinel against apoptosis induced by the NMDAR antagonist MK-801 in comparison to that elicited by clozapine and the mGlu2/3 agonist LY354740. These results suggest the potential therapeutic/prophylactic effect of rapastinel in ameliorating deleterious effects induced by NMDAR blockade during neurodevelopment.