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Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.

Dong LD, Chen J, Li F, Gao F, Wu J, Miao Y, Wang Z - Neural Plast. (2013)

Bottom Line: Moreover, expression of Cdk5, p35 and ratio of p-NR2A(S1232)/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; Institute of Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.

ABSTRACT
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-NR2A(S1232)/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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Changes of IOPs in C57BL/6 and DBA/2J mice at various ages. Bar chart showing changes of the average IOPs in C57BL/6 and DBA/2J mice at ages of 3 (n = 24), 6 (n = 18), 9 (n = 12) and 12 (n = 6) months. All data are presented as mean ± S.E.M. ***P < 0.001 versus 3-month-old C57BL/6 mice; ###P < 0.001 versus age-matched C57BL/6 mice.
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fig1: Changes of IOPs in C57BL/6 and DBA/2J mice at various ages. Bar chart showing changes of the average IOPs in C57BL/6 and DBA/2J mice at ages of 3 (n = 24), 6 (n = 18), 9 (n = 12) and 12 (n = 6) months. All data are presented as mean ± S.E.M. ***P < 0.001 versus 3-month-old C57BL/6 mice; ###P < 0.001 versus age-matched C57BL/6 mice.

Mentions: We first monitored changes in IOPs of DBA/2J mice with time. As shown in Figure 1, the average IOP of DBA/2J mice was 14.8 ± 0.5 mm Hg (n = 24) at age of 3 months, which was comparable to that of age-matched C57BL/6 control mice (13.6 ± 0.6 mm Hg) (n = 24). The average IOP of control mice kept this level at ages of 6, 9, and 12 months, while that of DBA/2J mice significantly increased to 18.5 ± 0.9 mm Hg (n = 18, P < 0.001) and 19.9 ± 1.0 mm Hg (n = 12, P < 0.001) at ages of 6 and 9 months, respectively, and then declined to 15.6 ± 0.8 mm Hg (n = 6, P > 0.05) at age of 12 months (Figure 1). In the present study, all of the DBA/2J mice showed progressive elevated IOPs. Therefore, our data included all animals.


Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.

Dong LD, Chen J, Li F, Gao F, Wu J, Miao Y, Wang Z - Neural Plast. (2013)

Changes of IOPs in C57BL/6 and DBA/2J mice at various ages. Bar chart showing changes of the average IOPs in C57BL/6 and DBA/2J mice at ages of 3 (n = 24), 6 (n = 18), 9 (n = 12) and 12 (n = 6) months. All data are presented as mean ± S.E.M. ***P < 0.001 versus 3-month-old C57BL/6 mice; ###P < 0.001 versus age-matched C57BL/6 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3794641&req=5

fig1: Changes of IOPs in C57BL/6 and DBA/2J mice at various ages. Bar chart showing changes of the average IOPs in C57BL/6 and DBA/2J mice at ages of 3 (n = 24), 6 (n = 18), 9 (n = 12) and 12 (n = 6) months. All data are presented as mean ± S.E.M. ***P < 0.001 versus 3-month-old C57BL/6 mice; ###P < 0.001 versus age-matched C57BL/6 mice.
Mentions: We first monitored changes in IOPs of DBA/2J mice with time. As shown in Figure 1, the average IOP of DBA/2J mice was 14.8 ± 0.5 mm Hg (n = 24) at age of 3 months, which was comparable to that of age-matched C57BL/6 control mice (13.6 ± 0.6 mm Hg) (n = 24). The average IOP of control mice kept this level at ages of 6, 9, and 12 months, while that of DBA/2J mice significantly increased to 18.5 ± 0.9 mm Hg (n = 18, P < 0.001) and 19.9 ± 1.0 mm Hg (n = 12, P < 0.001) at ages of 6 and 9 months, respectively, and then declined to 15.6 ± 0.8 mm Hg (n = 6, P > 0.05) at age of 12 months (Figure 1). In the present study, all of the DBA/2J mice showed progressive elevated IOPs. Therefore, our data included all animals.

Bottom Line: Moreover, expression of Cdk5, p35 and ratio of p-NR2A(S1232)/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; Institute of Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.

ABSTRACT
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-NR2A(S1232)/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.

Show MeSH
Related in: MedlinePlus