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Blockade of endogenous neuraminidase leads to an increase of neuronal excitability and activity-dependent synaptogenesis in the rat hippocampus. Eur J Neurosci 2010 Dec;32(11):1889-96

Date

11/04/2010

Pubmed ID

21044183

DOI

10.1111/j.1460-9568.2010.07468.x

Scopus ID

2-s2.0-78649708532   14 Citations

Abstract

Polysialic acids are widely distributed in neuronal tissue. Due to their position on glycoproteins and gangliosides on the outer cell membranes and anionic nature, polysialic acids are involved in multiple cell signaling events. The level of sialylation of the cellular surface is regulated by endogenous neuraminidase (NEU), which catalyses the hydrolysis of terminal sialic acid residues. Using the specific blocker of endogenous NEU, N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA), we show that downregulation of the endogenous NEU activity causes a significant increase in the level of hippocampal tissue sialylation. Acute application of NADNA increased the firing frequency and amplitude of spontaneous synchronous oscillations, and frequency of multiple unit activity in cultured hippocampal slices. The tonic phase of seizure-like activity in the low-magnesium model of ictogenesis was significantly increased in slices pretreated with NADNA. These data indicate that the degree of synchronization is influenced by the amount of active NEU in cultured hippocampal slices. Pretreatment with NADNA led to an increase of the density of simple and perforated synapses in the hippocampal CA1 stratum radiatum region. Co-incubation of slices with NADNA and high concentrations of calcium eliminated the effect of the NEU blocker on synaptic density, suggesting that synaptogenesis observed following downregulation of the endogenous NEU activity is an activity-dependent process.

Author List

Isaeva E, Lushnikova I, Savrasova A, Skibo G, Holmes GL, Isaev D

Author

Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Electrophysiology
Hippocampus
N-Acetylneuraminic Acid
Neuraminic Acids
Neuraminidase
Neurons
Rats
Rats, Wistar
Synapses
Tissue Culture Techniques