CaMKIIα knockout protects from ischemic neuronal cell death after resuscitation from cardiac arrest.

CaMKIIα knockout protects from ischemic neuronal cell death after resuscitation from cardiac arrest.
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CaMKIIα敲除可防止心脏骤停复苏后缺血性神经元细胞死亡。

DOI:
10.1016/j.brainres.2021.147699
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发表时间:
2021-12-15
期刊:
影响因子:
2.9
通讯作者:
Bayer KU
Bayer KU
中科院分区:
医学3区
文献类型:
--
作者:
Rumian NL;Chalmers NE;Tullis JE;Herson PS;Bayer KU

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CaMKIIα在突触可塑性中起双重作用,因为它可以介导相反方向的突触变化。我们假设CaMKIIα在神经元细胞死亡和存活中也发挥类似的双重作用。事实上,CaMKII抑制剂tatCN 21在兴奋性毒性/缺血性损伤期间或之后加入时是神经保护性的,但被描述为在这种损伤之前长期应用时引起致敏。然而,当在神经元培养物中比较几种不同抑制剂的长期CaMKII抑制时,我们没有检测到任何致敏作用。同样,在小鼠体内全脑缺血模型中(心脏骤停,随后进行心肺复苏),神经元CaMKIIα亚型的完全敲除不会引起致敏作用,而是显著的神经保护作用。
CaMKIIα plays a dual role in synaptic plasticity, as it can mediate synaptic changes in opposing directions. We hypothesized that CaMKIIα plays a similar dual role also in neuronal cell death and survival. Indeed, the CaMKII inhibitor tatCN21 is neuroprotective when added during or after excitotoxic/ischemic insults, but was described to cause sensitization when applied long-term prior to such insult. However, when comparing long-term CaMKII inhibition by several different inhibitors in neuronal cultures, we did not detect any sensitization. Likewise, in a mouse in vivo model of global cerebral ischemia (cardiac arrest followed by cardiopulmonary resuscitation), complete knockout of the neuronal CaMKIIα isoform did not cause sensitization but instead significant neuroprotection.
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发表时间: 2011-07
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