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Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices
Joint Authors
Laurier-Laurin, Marie-Elaine
Attiori Essis, Suzanne
Cyr, Michel
Massicotte, Guy
De Montigny, Audrée
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-09-08
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The lysosomal acid ceramidase, an enzyme known to limit intracellular ceramide accumulation, has been reported to be defective in neurodegenerative disorders.
We show here that rat hippocampal slices, preincubated with the acid ceramidase inhibitor (ACI) d-NMAPPD, exhibit increased N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in CA1 synapses.
The ACI by itself did not interfere with either paired pulse facilitation or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated fEPSPs, indicating that its influence on synaptic transmission is postsynaptic in origin and specific to the NMDA subtype of glutamate receptors.
From a biochemical perspective, we observed that Tau phosphorylation at the Ser262 epitope was highly increased in hippocampal slices preincubated with the ACI, an effect totally prevented by the global NMDA receptor antagonist D/L(−)-2-amino-5-phosphonovaleric acid (AP-5), the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), and the GluN2B (but not the GluN2A) receptor antagonist RO25-6981.
On the other hand, preincubation of hippocampal slices with the compound KN-62, an inhibitor known to interfere with calcium/calmodulin-dependent protein kinase II (CaMKII), totally abolished the effect of ACI on Tau phosphorylation at Ser262 epitopes.
Collectively, these results provide experimental evidence that ceramides play an important role in regulating Tau phosphorylation in the hippocampus via a mechanism dependent on GluN2B receptor subunits and CaMKII activation.
American Psychological Association (APA)
Laurier-Laurin, Marie-Elaine& De Montigny, Audrée& Attiori Essis, Suzanne& Cyr, Michel& Massicotte, Guy. 2014. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices. Neural Plasticity،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-1046651
Modern Language Association (MLA)
Laurier-Laurin, Marie-Elaine…[et al.]. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices. Neural Plasticity No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-1046651
American Medical Association (AMA)
Laurier-Laurin, Marie-Elaine& De Montigny, Audrée& Attiori Essis, Suzanne& Cyr, Michel& Massicotte, Guy. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices. Neural Plasticity. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-1046651
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1046651