Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory.

Akira Minami,Shou Mamada,Tomoya Hikita,Daisuke Ieno,Masakazu Saito,Takashi Suzuki,Kiyoshi Ikeda,Tadamune Otsubo,Tadanobu Takahashi,Manabu Sakakibara

doi:10.1371/journal.pone.0165257

Akira Minami, Shou Mamada + Show 8 more

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https://doi.org/10.1371/journal.pone.0165257

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Abstract

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.

Highlights

Sialic acid, an acidic monosaccharide, is expressed most frequently at the ends of glycans and creates a negative charge on the cell surface
Many neural functions including memory processing depend on sialic acid in glycoproteins and gangliosides [1,2,3]
Sialic acid contained in gangliosides such as the tetra-sialoganglioside GQ1b is crucial for synaptic plasticity and hippocampal memory [4, 5]

Summary

Introduction

An acidic monosaccharide, is expressed most frequently at the ends of glycans and creates a negative charge on the cell surface. Many neural functions including memory processing depend on sialic acid in glycoproteins and gangliosides [1,2,3]. Sialic acid contained in gangliosides such as the tetra-sialoganglioside GQ1b is crucial for synaptic plasticity and hippocampal memory [4, 5]. The sialic acid polymer (poly sialic acid, PSA), having a large. Role of Sialidase in LTP at Mossy Fiber-CA3 and Hippocampal Memory

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Conclusion