Increased expression of PAD2 after repeated intracerebroventricular infusions of soluble Abeta(25-35) in the Alzheimer's disease model rat brain: effect of memantine.
Increased expression of PAD2 after repeated intracerebroventricular infusions of soluble Abeta(25-35) in the Alzheimer's disease model rat brain: effect of memantine.
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DOI：
10.2478/s11658-009-0029-x
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发表时间：
2009
影响因子：
8.3
通讯作者：
Kato T
中科院分区：
文献类型：
--
作者：
Arif M;Kato T
肽基精氨酸脱亚胺酶（PAD）以Ca 2+依赖性方式将蛋白质中的精氨酸残基转化为瓜氨酸残基。我们以前的研究表明，双侧注射鹅膏蕈氨酸到大细胞基底核大鼠海马和纹状体的PAD 2活性升高。在这项研究中，我们研究了反复脑室内输注可溶性Aβ25-35是否会影响大鼠大脑任何区域的PAD 2表达。我们还评估了美金刚对Aβ诱导的PAD 2改变的保护作用。Aβ25-35的输注增加了海马中PAD 2的活性和蛋白水平，并且与美金刚共同处理抑制了这些变化。免疫组化分析显示，PAD 2的水平增加与GFAP阳性星形胶质细胞和CD 11b阳性小胶质细胞相一致。此外，免疫荧光染色显示瓜氨酸阳性免疫反应与GFAP阳性星形胶质细胞的出现相一致。与美金刚共处理逆转了星形胶质细胞和小胶质细胞的活化，从而减弱了PAD 2的增量。这些生化和免疫组化结果表明，PAD 2可能在早期阿尔茨海默病的病理学中发挥重要作用，并可能与美金刚治疗恢复的神经胶质细胞的变化相关。
Peptidylarginine deiminases (PADs) convert the arginine residues in proteins into citrulline residues in a Ca2+-dependent manner. We previously showed that a bilateral injection of ibotenic acid into the rat nucleus basalis magnocellularis elevated the PAD2 activity in the hippocampus and striatum. In this study, we examined whether repeated intracerebroventricular infusions of soluble Aβ25–35 would affect the PAD2 expression in any regions of the rat brain. We also assessed the protective effect of memantine on Aβ-induced PAD2 alterations. The infusion of Aβ25–35 increased the activity and protein level of PAD2 in the hippocampus, and co-treatment with memantine suppressed these changes. An immunohistochemical analysis showed that an increased level of PAD2 was coincident with GFAP-positive astrocytes and CD11b-positive microglia. In addition, immunofluoresecence staining revealed that citrullinepostive immunoreactivity coincided with the occurrence of GFAP-positive astrocytes. Co-treatment with memantine reversed the activation of the astrocytes and microglia, thus attenuating the PAD2 increment. These biochemical and immunohistochemical results suggest that PAD2 might play an important role in the pathology of early Alzheimer’s disease, and may correlate with the changes in glial cells that are recovered by memantine treatment.