Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome.
Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome.
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DOI：
10.1016/j.bbadis.2010.06.015
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
Jope, Richard S.
中科院分区：
文献类型：
--
作者：
Yuskaitis, Christopher J.;Beurel, Eleonore;Jope, Richard S.
脆性X综合征（FXS）是遗传性精神发育迟滞的最常见形式，也是少数已知的自闭症遗传原因之一。FXS是由Fmr 1基因功能丧失引起的，因此Fmr 1基因敲除小鼠提供了一个研究FXS和自闭症相关损伤的模型，并测试了潜在的治疗干预措施。抑制性糖原合成酶激酶-3（GSK 3）的丝氨酸磷酸化在Fmr 1敲除小鼠的脑区比野生型小鼠低，GSK 3抑制剂锂挽救了Fmr 1敲除小鼠的几种行为障碍。因此，我们研究了是否在Fmr 1基因敲除小鼠的GSK 3丝氨酸磷酸化也改变了脑外，如果管理锂改善了巨睾症表型。此外，由于GSK 3调节免疫系统的许多功能，并且免疫改变与自闭症有关，我们测试了Fmr 1敲除小鼠的免疫功能是否改变。抑制性丝氨酸磷酸化的GSK 3在睾丸和肝脏的Fmr 1基因敲除小鼠比野生型小鼠显着降低，和慢性锂治疗减少在Fmr 1基因敲除小鼠的巨睾症。在Fmr 1基因敲除小鼠中未发现外周免疫功能的改变。然而，检查神经胶质细胞，大脑的免疫细胞，发现在Fmr 1基因敲除小鼠的几个大脑区域中有反应性星形胶质细胞，锂治疗减少了纹状体和小脑中的反应性星形胶质细胞。这些结果提供了FXS中GSK 3失调参与的进一步证据，并证明锂给药减少了Fmr 1敲除小鼠中的巨睾症和反应性星形胶质细胞。
Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is one of the few known genetic causes of autism. FXS results from the loss of Fmr1 gene function, thus Fmr1 knockout mice provide a model to study impairments associated with FXS and autism and to test potential therapeutic interventions. The inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3) is lower in brain regions of Fmr1 knockout mice than wild-type mice and the GSK3 inhibitor lithium rescues several behavioral impairments in Fmr1 knockout mice. Therefore, we examined if the serine-phosphorylation of GSK3 in Fmr1 knockout mice also was altered outside the brain and if administration of lithium ameliorated the macroorchidism phenotype. Additionally, since GSK3 regulates numerous functions of the immune system and immune alterations have been associated with autism, we tested if immune function is altered in Fmr1 knockout mice. The inhibitory serine-phosphorylation of GSK3 was significantly lower in the testis and liver of Fmr1 knockout mice than wild-type mice, and chronic lithium treatment reduced macroorchidism in Fmr1 knockout mice. No alterations in peripheral immune function were identified in Fmr1 knockout mice. However, examination of glia, the immune cells of the brain, revealed reactive astrocytes in several brain regions of Fmr1 knockout mice and treatment with lithium reduced this in the striatum and cerebellum. These results provide further evidence of the involvement of dysregulated GSK3 in FXS, and demonstrate that lithium administration reduces macroorchidism and reactive astrocytes in Fmr1 knockout mice.
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影响因子：
4.8
作者：
Beurel, Eleonore;Jope, Richard S.
通讯作者：
Jope, Richard S.
影响因子：
9.3
作者：
Beurel E;Jope RS
通讯作者：
Jope RS
影响因子：
25
作者：
Belmonte, Matthew K.;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
DOI：
10.1097/dbp.0b013e31817dc447
发表时间：
2008-08-01
影响因子：
2.4
作者：
Berry-Kravis, Elizabeth;Sumis, Allison;Greenough, William T.
通讯作者：
Greenough, William T.
影响因子：
16.8
作者：
Beurel E;Michalek SM;Jope RS
通讯作者：
Jope RS