ArticlePsychopharmacology2018
Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.
Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 35 citations in OpenAlex.
- Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development.Journal of neurochemistry · 2025Review
- Investigation on Inhibiting SPHK - S1P Pathway to Improve ADHD Model Rats Behavior via Lipidomics.Neuropsychiatric disease and treatment · 2025Article
- Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.Journal of molecular neuroscience : MN · 2024Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Exome-wide analysis identify multiple variations in olfactory receptor genes (Frontiers in medicine · 2023Article
- Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model.International journal of molecular sciences · 2022Article
- Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism.Psychopharmacology · 2022Article
- Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives.Journal of molecular neuroscience : MN · 2022Review
- Sex Differences in Spatial Learning and Memory in Valproic Acid Rat Model of Autism: Possible Beneficial Role of Exercise Interventions.Frontiers in behavioral neuroscience · 2022Article
- Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder.Open biology · 2021Article
- Oxytocin Differentiated Effects According to the Administration Route in a Prenatal Valproic Acid-Induced Rat Model of Autism.Medicina (Kaunas, Lithuania) · 2020Article
- mTOR Suppresses Macroautophagy During Striatal Postnatal Development and Is Hyperactive in Mouse Models of Autism Spectrum Disorders.Frontiers in cellular neuroscience · 2020Article
- Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis.Journal of Zhejiang University. Science. BArticle
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAutism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, 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.
objectiveThe objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism.
methodsWe 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.
resultsWe 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 autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus.
conclusionWe have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.
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