A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.
A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.
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DOI：
10.1371/journal.pone.0126856
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发表时间：
2015
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：
Nabeka H;Shimokawa T;Doihara T;Saito S;Wakisaka H;Hamada F;Kobayashi N;Matsuda S
四种鞘脂激活蛋白（即皂苷a - d）由单一前体蛋白丙皂苷（PS）合成，在体内和体外均产生外源性神经营养作用。Kainic acid （KA）是研究鼠类神经营养因子升高的良好模型；在该动物模型中，神经元和脉络膜丛中PS及其mRNA升高。来源于PS神经营养区的18-mer肽（LSELIINNATEELLIKGL; PS18）可防止缺血后的神经元损伤，PS18是一种有效的候选分子，可用于减轻缺血诱导的学习障碍和神经元损失。KA是一种谷氨酸类似物，刺激兴奋性神经递质释放并诱导缺血样神经元变性；它已被用来定义涉及神经变性和神经保护的机制。在本研究中，我们证明皮下注射0.2和2.0 mg/kg PS18可显著改善Wistar大鼠的行为缺陷（每组n = 6），并提高海马和皮质神经元对12 mg/kg KA诱导的神经毒性的存活率。PS18显著保护海马突触免受ka诱导的破坏。为了评估PS18-和ka在这些海马区域诱导作用的程度，我们使用甲苯胺蓝染色的半薄切片以及苏木精和伊红染色的有序切片进行组织学评估。我们揭示了KA诱导的脑损伤的一个独特特征，据报道，它模仿缺血，但影响的区域比缺血诱导的损伤大得多：KA诱导的神经元变性不仅在CA1区域，神经元在缺血后变性，而且在CA2， CA3和CA4海马区域。
Four sphingolipid activator proteins (i.e., saposins A–D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.
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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：
HEGGLI, DE;AAMODT, A;MALTHESORENSSEN, D
通讯作者：
MALTHESORENSSEN, D
影响因子：
3.7
作者：
Gao HL;Li C;Nabeka H;Shimokawa T;Kobayashi N;Saito S;Wang ZY;Cao YM;Matsuda S
通讯作者：
Matsuda S
DOI：
10.1073/pnas.89.23.11254
发表时间：
1992-12-01
影响因子：
11.1
作者：
HIRAIWA, M;SOEDA, S;OBRIEN, JS
通讯作者：
OBRIEN, JS
DOI：
10.1006/bbrc.1996.1869
发表时间：
1996-12-24
影响因子：
3.1
作者：
Campana, WM;Hiraiwa, M;OBrien, JS
通讯作者：
OBrien, JS