Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory.
Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory.
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DOI：
10.1371/journal.pone.0165257
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Minami A;Saito M;Mamada S;Ieno D;Hikita T;Takahashi T;Otsubo T;Ikeda K;Suzuki T
唾液酸与糖脂和糖蛋白中的多糖结合，对突触的可塑性和记忆是必不可少的。唾液酸酶(EC 3.2.1.18)具有Neu1、Neu2、Neu3和Neu4四种同工酶，通过从唾液酸偶联物中去除唾液酸来调节糖链的唾液酸化水平。在本研究中，我们研究了唾液酸酶活性在大鼠海马区的分布以及唾液酸酶在海马区记忆加工中的作用。我们之前开发了一种高灵敏的唾液酸酶活性组织化学成像探针BTP3-Neu5Ac。BTP3-Neu5Ac可被大鼠Neu2和Neu4以及Neu1和Neu3在pH 7.3时有效切割。用BTP3-Neu5Ac在pH 7.3的条件下对大鼠海马急性切片进行染色，苔藓纤维终末区显示出较强的唾液酸酶活性。因此，在苔藓纤维终末区域，研究了唾液酸酶在突触可塑性中的作用。唾液酸酶抑制剂2，3-脱氢-2-脱氧-N-乙酰神经氨酸(DANA)可抑制苔藓纤维-CA3锥体细胞突触的长时程增强(LTP)。在LTP诱导后，DANA也不能降低双脉冲易化作用。我们还利用Morris水迷宫研究了唾液酸酶在海马区依赖的空间记忆中的作用。海马CA3区注射达那普利或敲除Neu4均可延长小鼠到达平台的潜伏期，但不影响运动能力。结果表明，Neu4对唾液酸化信号的调节参与了海马神经元的记忆加工。
Sialic acid bound to glycans in glycolipids and glycoproteins is essential for synaptic plasticity and memory. Sialidase (EC 3.2.1.18), which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate. In the present study, we investigated the distribution of sialidase activity in rat hippocampus and the role of sialidase in hippocampal memory processing. We previously developed a highly sensitive histochemical imaging probe for sialidase activity, BTP3-Neu5Ac. BTP3-Neu5Ac was cleaved efficiently by rat Neu2 and Neu4 at pH 7.3 and by Neu1 and Neu3 at pH 4.6. When a rat hippocampal acute slice was stained with BTP3-Neu5Ac at pH 7.3, mossy fiber terminal fields showed relatively intense sialidase activity. Thus, the role of sialidase in the synaptic plasticity was investigated at mossy fiber terminal fields. The long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses was impaired by 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA), a sialidase inhibitor. DANA also failed to decrease paired-pulse facilitation after LTP induction. We also investigated the role of sialidase in hippocampus-dependent spatial memory by using the Morris water maze. The escape latency time to reach the platform was prolonged by DANA injection into the hippocampal CA3 region or by knockdown of Neu4 without affecting motility. The results show that the regulation of sialyl signaling by Neu4 is involved in hippocampal memory processing.