Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse
Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse
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DOI：
10.1038/jcbfm.2008.8
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发表时间：
2008-06-01
影响因子：
6.3
通讯作者：
Mattiasson, Gustav
中科院分区：
文献类型：
--
作者：
Deierborg, Tomas;Wieloch, Tadeusz;Mattiasson, Gustav
亚致死性缺血后大脑中解偶联蛋白 2 (UCP2) 上调，并且 UCP2 的过度表达在多种神经退行性疾病模型中具有神经保护作用。我们通过将过度表达 UCP2 (UCP2/3tg) 的小鼠和野生型同窝小鼠 (wt) 置于 12 分钟的整体脑缺血中，研究了 UCP2 水平的增加是否会减少全脑缺血后的神经元损伤。在恢复 4 天时评估皮层、海马、纹状体和丘脑的组织病理学结果，使选择性神经元死亡成熟。全脑缺血导致纹状体、丘脑、CA1 和 CA2 中广泛的细胞死亡，以及 CA3 和齿状回 (DG) 海马亚区中不太明显的细胞死亡。与野生型相比，UCP2/3tg 动物的腹侧后外侧 VPL 和内侧 VPM 丘脑核的组织学损伤显着较低。相对于未受保护的DG，与野生型动物相比，这些丘脑区域在UCP2/3tg中显示出更大的UCP2表达增加。在其他研究区域中，UCP2/3tg 动物的组织学损伤低于或等于 wt。因此，丘脑的神经保护作用与 UCP2 的高表达相关，UCP2 在许多神经退行性疾病模型中具有神经保护作用。
Uncoupling protein 2 (UCP2) is upregulated in the brain after sublethal ischemia, and overexpression of UCP2 is neuroprotective in several models of neurodegenerative disease. We investigated if increased levels of UCP2 diminished neuronal damage after global brain ischemia by subjecting mice overexpressing UCP2 (UCP2/3tg) and wild-type littermates (wt) to a 12-min global ischemia. The histopathological outcome in the cortex, hippocampus, striatum, and thalamus was evaluated at 4 days of recovery, allowing maturation of the selective neuronal death. Global ischemia led to extensive cell death in the striatum, thalamus, and in the CA1 and CA2, and less-pronounced cell death in the CA3 and dentate gyrus (DG) hippocampal subfields. Histologic damage was significantly lower in the ventral posterolateral VPL and medial VPM thalamic nuclei in UCP2/3tg animals compared with wt. These thalamic regions showed a larger increase in UCP2 expression in UCP2/3tg compared with wt animals relative to the nonprotected DG. In the other regions studied, the histologic damage was lower or equal in UCP2/3tg animals compared with wt. Consequently, neuroprotection in the thalamus correlated with a high expression of UCP2, which is neuroprotective in a number of models of neurodegenerative diseases.