The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

Abstract

Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac.

Keywords: BTP3-Neu5Ac; BTP9-Neu5Ac; diabetes; elastin; glutamate; hippocampus; memory; pancreas; sialidase; skin; virus.

Figure 1

The rapid increase in sialidase activity in conjunction with neural activity. (A) Staining principles of BTP3-Neu5Ac. (B) Staining of rat hippocampal CA3 with BTP3-Neu5Ac. St, striatum. Scale, 0.1 mm. (C) Changes in sialidase activity at striatum lucidum by stimulation of the hippocampal mossy fibers (100 Hz, 5 s).

Figure 2

Sialic acid desorption during memory formation. (A) In vivo monitoring of sialic acid desorption using a microdialysis method. (B,C) Increase in the amount of sialic acid in the extracellular fluid of the rat hippocampus by depolarizing stimulation (B) or during context learning with fear conditioning (C) (* p < 0.05, vs. basal level).

Figure 3

Effects of the sialidase inhibitor DANA on the release of glutamate and insulin. (A) Negative feedback on neural excitation by sialidase. DANA promotes the release of glutamate. (B) Distribution of sialidase activity in the mouse pancreas (left, scale, 0.1 mm). DANA promotes insulin secretion (right). Glc, glucose; GLP-1R, glucagon-like peptide-1 receptor; GLUT2, glucose transporter 2; KATP, ATP-sensitive potassium channel; SUR, sulfonylurea receptor; VDCC, voltage-dependent calcium channel.