Decrease in prosaposin in the Dystrophic mdx mouse brain.
Decrease in prosaposin in the Dystrophic mdx mouse brain.
复制标题
DOI：
10.1371/journal.pone.0080032
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Matsuda S
中科院分区：
文献类型：
--
作者：
Gao HL;Li C;Nabeka H;Shimokawa T;Kobayashi N;Saito S;Wang ZY;Cao YM;Matsuda S
Duchenne肌营养不良症是由X连锁的dystrophin基因突变引起的，会导致大脑的代谢和结构紊乱。大脑结构中缺乏营养不良蛋白与认知功能受损有关。丙皂苷(PS)是一种神经营养因子，广泛存在于脉络丛和各种脑区。我们调查了PS是否在Dstrophin丢失和大体和/或超微结构脑异常之间起到了联系。用免疫组织化学、Western blotting和原位杂交等方法研究了幼年和成年mdx小鼠脑内PS的分布。免疫组织化学显示mdx鼠大脑皮层、海马区、小脑和脉络丛神经元胞浆中PS含量较低。Western blotting证实，无论是青少年还是成年人，这些脑区的PS水平都较低。即使脉络丛产生的PS较低，脑脊液(CSF)的PS也没有明显下降。原位杂交结果显示，正常小鼠和mdx小鼠PS mRNA的初级形态均为分泌型PS，mdx小鼠上述脑区的Pro+9杂交信号弱于正常小鼠。我们还研究了丝裂原活化蛋白激酶信号。MDX小鼠体内ERK1/2活性较强，ERK1/2活性与PS活性呈正相关，外源PS18对SH-SY5Y细胞中的p-ERK1/2和PS均有刺激作用。低水平的PS及其受体提示PS参与了MDX小鼠脑内的某些病理变化。
Duchenne muscular dystrophy caused by a mutation in the X-linked dystrophin gene induces metabolic and structural disorders in the brain. A lack of dystrophin in brain structures is involved in impaired cognitive function. Prosaposin (PS), a neurotrophic factor, is abundant in the choroid plexus and various brain regions. We investigated whether PS serves as a link between dystrophin loss and gross and/or ultrastructural brain abnormalities. The distribution of PS in the brains of juvenile and adult mdx mice was investigated by immunochemistry, Western blotting, and in situ hybridization. Immunochemistry revealed lower levels of PS in the cytoplasm of neurons of the cerebral cortex, hippocampus, cerebellum, and choroid plexus in mdx mice. Western blotting confirmed that PS levels were lower in these brain regions in both juveniles and adults. Even with low PS production in the choroids plexus, there was no significant PS decrease in cerebrospinal fluid (CSF). In situ hybridization revealed that the primary form of PS mRNA in both normal and mdx mice was Pro+9, a secretory-type PS, and the hybridization signals for Pro+9 in the above-mentioned brain regions were weaker in mdx mice than in normal mice. We also investigated mitogen-activated protein kinase signalling. Stronger activation of ERK1/2 was observed in mdx mice, ERK1/2 activity was positively correlated with PS activity, and exogenous PS18 stimulated both p-ERK1/2 and PS in SH-SY5Y cells. Low levels of PS and its receptors suggest the participation of PS in some pathological changes in the brains of mdx mice.
登录
查看更多内容
影响因子：
2.9
作者：
Chen, Jie;Saito, Shouichiro;Matsuda, Seiji
通讯作者：
Matsuda, Seiji
影响因子：
2.9
作者：
COLLARD, MW;SYLVESTER, SR;GRISWOLD, MD
通讯作者：
GRISWOLD, MD
影响因子：
3.6
作者：
Hosoda, Yoshiki;Miyawaki, Kyojy;Matsuda, Seiji
通讯作者：
Matsuda, Seiji
DOI：
10.1073/pnas.94.9.4778
发表时间：
1997-04-29
影响因子：
11.1
作者：
Hiraiwa, M;Taylor, EM;OBrien, JS
通讯作者：
OBrien, JS
影响因子：
64.5
作者：
HOFFMAN, EP;BROWN, RH;KUNKEL, LM
通讯作者：
KUNKEL, LM