Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism

Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in... Rationale Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early child- hood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. Objective The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. Methods We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. Results We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism

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Publisher
Springer Journals
Copyright
Copyright © 2017 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Neurosciences; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
D.O.I.
10.1007/s00213-017-4805-4
Publisher site
See Article on Publisher Site

Abstract

Rationale Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early child- hood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. Objective The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. Methods We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. Results We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and

Journal

PsychopharmacologySpringer Journals

Published: Dec 7, 2017

References

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