Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.
Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.
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DOI：
10.1155/2013/670254
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发表时间：
2013
影响因子：
3.1
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Dong LD;Chen J;Li F;Gao F;Wu J;Miao Y;Wang Z
DBA/2J小鼠已被用作自发性继发性青光眼的模型。在此，我们用Western印迹技术研究了DBA/2J小鼠视网膜中NMDAR亚单位和CDK5/p35/NMDAR信号的表达变化。6~12月龄DBA/2J小鼠视网膜中NR1和NR2A亚基的蛋白水平与同龄C57BL/6小鼠无明显差异。相反，与年龄匹配的对照组相比，DBA/2J小鼠在6个月和9个月时，随着眼压(IOP)的升高，NR2B亚单位的蛋白水平除了随年龄的变化而显著增加。此外，CDK5、p35的表达和p-NR2AS1232/NR2A的比值随着时间的延长而逐渐升高，提示CDK5/p35信号通路被激活。然而，除了DBA/2J小鼠在6个月时p35蛋白显著增加外，这些蛋白的变化在两个品系小鼠中都是相同的水平。同时，DBA/2J小鼠视网膜神经节细胞(RGC)标志物BRN-3a的蛋白水平在9~12个月时显著下降，与NR2B表达的变化相平行。我们的结果提示，高眼压诱导的NMDARs NR2B亚单位的表达增加可能参与了DBA/2J小鼠RGC的退变。
DBA/2J mouse has been used as a model for spontaneous secondary glaucoma. Here, we investigated changes in expression of NMDA receptor (NMDAR) subunits and Cdk5/p35/NMDAR signaling in retinas of DBA/2J mice using Western blot technique. The protein levels of NR1 and NR2A subunits in retinas of DBA/2J mice at all ages (6–12 months) were not different from those in age-matched C57BL/6 mice. In contrast, the protein levels of NR2B subunits, in addition to age-dependent change, significantly increased with elevated intraocular pressure (IOP) in DBA/2J mice at 6 and 9 months as compared with age-matched controls. Moreover, expression of Cdk5, p35 and ratio of p-NR2AS1232/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway. However, the changes in these proteins were in the same levels in both strain mice, except a significant increase of p35 proteins at 6 months in DBA/2J mice. Meanwhile, the protein levels of Brn-3a, a retinal ganglion cell (RGC) maker, remarkably decreased at 9–12 months in DBA/2J mice, which was in parallel with the changes of NR2B expression. Our results suggest that elevated IOP-induced increase in expression of NR2B subunits of NMDARs may be involved in RGC degeneration of DBA/2J mice.
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DOI：
10.1523/jneurosci.0203-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li S;Jin M;Koeglsperger T;Shepardson NE;Shankar GM;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
4.4
作者：
Hare, WA;WoldeMussie, E;Wheeler, L
通讯作者：
Wheeler, L
影响因子：
4.4
作者：
Ju WK;Kim KY;Angert M;Duong-Polk KX;Lindsey JD;Ellisman MH;Weinreb RN
通讯作者：
Weinreb RN
青光眼中的视网膜神经节细胞凋亡与眼内压和IOP诱导的细胞外基质有关。
影响因子：
4.4
作者：
Guo L;Moss SE;Alexander RA;Ali RR;Fitzke FW;Cordeiro MF
通讯作者：
Cordeiro MF
DBA/2J小鼠的进行性神经节细胞丧失和视神经变性是可变且不对称的。
影响因子：
2.4
作者：
Schlamp, Cassandra L.;Li, Yan;Dietz, Joel A.;Janssen, Katherine T.;Nickells, Robert W.
通讯作者：
Nickells, Robert W.