An approach to experimental synaptic pathology using green fluorescent protein-transgenic mice and gene knockout mice to show mitochondrial permeability transition pore-driven excitotoxicity in interneurons and motoneurons.
An approach to experimental synaptic pathology using green fluorescent protein-transgenic mice and gene knockout mice to show mitochondrial permeability transition pore-driven excitotoxicity in interneurons and motoneurons.
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DOI：
10.1177/0192623310389475
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发表时间：
2011-01
影响因子：
1.5
通讯作者：
Martin LJ
中科院分区：
文献类型：
--
作者：
Martin LJ
研究人员使用表达增强型绿色荧光蛋白（eGFP）的转基因小鼠，由甘氨酸转运蛋白-2基因启动子驱动，以特异性地可视化甘氨酸能中间神经元，或同源框-9（Hb 9）基因启动子来可视化运动神经元，以评估它们对体内兴奋性毒素的脆弱性。用特异性N-甲基-D-天冬氨酸（NMDA）受体激动剂喹啉酸（QA）和非NMDA离子通道谷氨酸受体激动剂红藻氨酸（KA）在成年雄性和雌性小鼠腰髓中造成立体定位兴奋毒性损伤。QA和KA诱导脊髓甘氨酸能中间神经元大规模变性。甘氨酸能中间神经元比运动神经元对NMDA受体介导的和非NMDA谷氨酸受体介导的兴奋性毒性更敏感。脊髓兴奋性中毒后的结果是性别依赖性的，男性比女性表现出更大的敏感性。脊髓中间神经元的兴奋性毒性变性类似于细胞凋亡，而运动神经元变性则表现为非细胞凋亡。核周线粒体积累是前的NMDA和非NMDA受体介导的兴奋性毒性刺激的中间神经元和运动神经元。亲环素D的基因消融，线粒体通透性转换孔（mPTP）的调节，保护中间神经元和运动神经元兴奋性毒性。结果表明，在成年小鼠脊髓中，甘氨酸能中间神经元比运动神经元对刺激线粒体积累的兴奋性毒性更敏感，并且mPTP具有促死亡功能，介导体内凋亡和非凋亡神经元变性。
Researchers used transgenic mice expressing enhanced-green fluorescent protein (eGFP) driven by either the glycine transporter-2 gene promoter to specifically visualize glycinergic interneurons or the homeobox-9 (Hb9) gene promoter to visualize motoneurons for assessing their vulnerabilities to excitotoxins in vivo. Stereotaxic excitotoxic lesions were made in adult male and female mouse lumbar spinal cord with the specific N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid (QA) and the non-NMDA ion channel glutamate receptor agonist kainic acid (KA). QA and KA induced large-scale degeneration of glycinergic interneurons in spinal cord. Glycinergic interneurons were more sensitive than motoneurons to NMDA receptor-mediated and non-NMDA glutamate receptor-mediated excitotoxicity. Outcome after spinal cord excitotoxicity was gender-dependent, with males showing greater sensitivity than females. Excitotoxic degeneration of spinal interneurons resembled apoptosis, while motoneuron degeneration appeared non-apoptotic. Perikaryal mitochondrial accumulation was antecedent to both NMDA and non-NMDA receptor-mediated excitotoxic stimulation of interneurons and motoneurons. Genetic ablation of cyclophilin D, a regulator of the mitochondrial permeability transition pore (mPTP), protected both interneurons and motoneurons from excitotoxicity. The results demonstrate in adult mouse spinal cord that glycinergic interneurons are more sensitive than motoneurons to excitotoxicity that stimulates mitochondrial accumulation, and that the mPTP has pro-death functions mediating apoptotic and non-apoptotic neuronal degeneration in vivo.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
64.8
作者：
CURTIS, DR;PHILLIS, JW;WATKINS, JC
通讯作者：
WATKINS, JC
影响因子：
5.5
作者：
ECCLES, JC;FATT, P;KOKETSU, K
通讯作者：
KOKETSU, K
影响因子：
6
作者：
Chang, Qing;Martin, Lee J.
通讯作者：
Martin, Lee J.
影响因子：
11.4
作者：
Barsoum, Mark J.;Yuan, Hua;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella