Over-expressed MST1 impaired spatial memory via disturbing neural oscillation patterns in mice.,Genes, Brain and Behavior

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Over-expressed MST1 impaired spatial memory via disturbing neural oscillation patterns in mice.
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2020-05-28 , DOI: 10.1111/gbb.12678
Yingchun Shang ₁ , Yuxing Yan ₁ , Bin Chen ₁ , Jianhai Zhang ₂ , Tao Zhang ₁

Affiliation

The activated mammalian Ste20‐like serine/threonine kinases 1 (MST1) was found in the central nervous system diseases, such as cerebral ischemia, stroke and ALS, which were related with cognitions. The aim of this study was to examine the effect of elevated MST1 on memory functions in C57BL/6J mice. We also explored the underlying mechanism about the pattern alteration of neural oscillations, closely associated with cognitive dysfunctions, at different physiological rhythms, which were related to a wide range of basic and higher‐level cognitive activities. A mouse model of the adeno‐associated virus (AAV)‐mediated overexpression of MST1 was established. The behavioral experiments showed that spatial memory was significantly damaged in MST1 mice. The distribution of either theta or gamma power was clearly disturbed in MST1 animals. Moreover, the synchronization in both theta and gamma rhythms, and theta‐gamma cross‐frequency coupling were significantly weakened in MST1 mice. In addition, the expressions of GABAA receptor, GAD67 and parvalbumin (PV) were obviously increased in MST1 mice. Meanwhile, blocking MST1 activity could inhibit the activation of FOXO3a and YAP. The above data suggest that MST1‐overexpression may induce memory impairments via disturbing the patterns of neural activities, which is possibly associated with the abnormal GABAergic expression level.

中文翻译：

通过扰乱小鼠的神经振荡模式，过表达的MST1损害了空间记忆。

被激活的哺乳动物Ste20样丝氨酸/苏氨酸激酶1（MST1）被发现与认知有关的中枢神经系统疾病，例如脑缺血，中风和ALS。这项研究的目的是检查MST1升高对C57BL / 6J小鼠记忆功能的影响。我们还探讨了在不同生理节律下与认知功能障碍密切相关的神经振荡模式改变的潜在机制，这与广泛的基础和高级认知活动有关。建立了腺相关病毒（AAV）介导的MST1过表达的小鼠模型。行为实验表明，MST1小鼠的空间记忆明显受损。在MST1动物中，θ或γ功率的分布明显受到干扰。此外，MST1小鼠的theta和gamma节奏的同步性以及theta-gamma跨频耦合均被明显削弱。此外，MST1小鼠中GABAA受体，GAD67和小白蛋白（PV）的表达明显增加。同时，阻断MST1活性可以抑制FOXO3a和YAP的激活。以上数据表明MST1过表达可能会通过干扰神经活动的模式而引起记忆障碍，这可能与GABA能表达水平异常有关。

更新日期：2020-07-23

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