Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?
Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?
复制标题
DOI：
10.1186/1750-1326-6-55
复制
发表时间：
2011-07-30
影响因子：
15.1
通讯作者：
Rodríguez JJ
中科院分区：
文献类型：
--
作者：
Olabarria M;Noristani HN;Verkhratsky A;Rodríguez JJ
星形胶质细胞是大脑稳态的基础，也是包括阿尔茨海默病（AD）在内的许多神经病变的进展和结果的基础。在AD （3xTg-AD）三重转基因小鼠模型中，普遍的海马星形胶质细胞萎缩先于限制性和特异性β-淀粉样蛋白（a β）斑块相关的星形胶质细胞增生。星形胶质细胞是中枢神经系统谷氨酸能传递的关键细胞，通过谷氨酸-谷氨酰胺穿梭维持谷氨酸的合成、摄取和转换，是谷氨酸稳态的主要元素。谷氨酰胺合成酶（GS）在星形胶质细胞中特异性表达，通过atp依赖的谷氨酸胺化形成谷氨酰胺。在这里，我们报道了3xTg-AD动物9 - 18月龄时海马两个主要认知区（齿状回、DG和CA1）中GS星形细胞表达的变化。我们发现，GS免疫反应（GS- ir）星形胶质细胞的Nv（细胞数/mm3）从12个月（28.59%）开始显著减少，并持续到18个月（31.65%）。gs阳性星形胶质细胞Nv在18月龄CA1降低（33.26%）。GS- ir星形胶质细胞Nv的减少与GS总表达的减少（由其光密度决定）相一致，在18个月时变得显著（DG和CA1分别为21.61%和19.68%）。GS-IR Nv的变化与a β沉积物的存在直接相关，在不含a β的地区下降了47.92%，而在不含a β的地区则下降了23.47%。含有星形胶质细胞的GS和GS免疫反应性的这些变化表明，在疾病的晚期和晚期，ad相关的谷氨酸稳态系统受损，这可能影响患病大脑中谷氨酸能传递的功效，从而可能导致认知缺陷。
Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm3) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.
登录
查看更多内容
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：
4.7
作者：
Deitmer, JW;Bröer, A;Bröer, S
通讯作者：
Bröer, S
影响因子：
4.2
作者：
McKenna, Mary C.
通讯作者：
McKenna, Mary C.
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
DOI：
10.1016/j.molbrainres.2004.02.021
发表时间：
2004-05-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Hughes, EG;Maguire, JL;Sutherland, ML
通讯作者：
Sutherland, ML