GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice
GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice
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DOI：
10.1097/fbp.0000000000000229
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发表时间：
2016-08
影响因子：
1.6
通讯作者：
Yunlan Ni;Wei Zhang;X. Bao;Wei Wang;Lu Song;Bo Jiang
中科院分区：
文献类型：
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作者：
Yunlan Ni;Wei Zhang;X. Bao;Wei Wang;Lu Song;Bo Jiang
认知缺陷是精神分裂症的核心症状，但仍然缺乏有效的治疗方法。已有研究报道脑源性神经营养因子（BDNF）信号通路与学习记忆密切相关。单唾液酸四己糖神经节苷脂（GM 1）是一种神经节苷脂，具有广泛的药理作用，可增强BDNF信号级联反应。本研究旨在评估GM 1对精神分裂症相关认知障碍的影响。使用MK 801短暂破坏N-甲基-D-天冬氨酸受体以产生精神分裂症认知缺陷的动物模型。结果发现，与对照组小鼠相比，MK 801处理组小鼠在不同的行为测试中表现出明显的记忆能力缺陷，并且这伴随着海马BDNF信号通路的减少。连续给予GM 1完全恢复了MK 801诱导的认知缺陷和海马中受损的BDNF信号传导。此外，BDNF系统抑制剂消除了GM 1在MK 801模型中的作用。综上所述，我们的研究结果表明，GM 1可以逆转MK 801诱导的认知障碍，这表明GM 1在治疗精神分裂症相关的认知障碍方面具有潜在的用途。
Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments.