title: Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing in rat hippocampus.
abstract: Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K+-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for sialic acid removal on the extracellular cell surface during neural excitation, the extracellular free sialic acid level in the hippocampus was monitored usingin vivomicrodialysis. The free sialic acid level was increased by high-K+-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Akira
authors.initials: A
authors.lastname: Minami
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Meguro
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ishibashi
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Ami
authors.initials: A
authors.lastname: Ishii
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Mako
authors.initials: M
authors.lastname: Shiratori
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Saki
authors.initials: S
authors.lastname: Sai
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Horii
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Hokuto
authors.initials: H
authors.lastname: Fukumoto
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Sumika
authors.initials: S
authors.lastname: Shimba
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Risa
authors.initials: R
authors.lastname: Taguchi
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Organic Chemistry, School of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure-shi, Hiroshima 737-0112, Japan.
authors.forename: Tadamune
authors.initials: T
authors.lastname: Otsubo
authors.affiliation: Department of Organic Chemistry, School of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure-shi, Hiroshima 737-0112, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: From the Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and suzukit@u-shizuoka-ken.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000201:enzymology*; D005260:Female; D008297:Male; D008568:Memory / Q000502:physiology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D017966:Pyramidal Cells / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid
keywords: hippocampus; imaging; rat; sialic acid; sialidase