Density of sphingosine-1-phosphate receptors is altered in cortical nerve-terminals of insulin-resistant Goto-Kakizaki rats and diet-induced obese mice

  • Sphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation. Moreover, S1P metabolism alterations have been reported in neurodegenerative disorders. We have previously reported that S1PRs are present in nerve terminals, exhibiting distinct sub-synaptic localization and neuromodulation actions. Since type 2 diabetes (T2D) causes synaptic dysfunction, we hypothesized that S1P signaling is modified in nerve terminals. In this study, we determined the density of S1PRs in cortical synaptosomes from insulin-resistant Goto-Kakizaki (GK) rats and Wistar controls, and from mice fed a high-fat diet (HFD) and low-fat-fed controls. Relative to their controls, GK rats showed similar cortical S1P concentration despite higher S1P levels inSphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation. Moreover, S1P metabolism alterations have been reported in neurodegenerative disorders. We have previously reported that S1PRs are present in nerve terminals, exhibiting distinct sub-synaptic localization and neuromodulation actions. Since type 2 diabetes (T2D) causes synaptic dysfunction, we hypothesized that S1P signaling is modified in nerve terminals. In this study, we determined the density of S1PRs in cortical synaptosomes from insulin-resistant Goto-Kakizaki (GK) rats and Wistar controls, and from mice fed a high-fat diet (HFD) and low-fat-fed controls. Relative to their controls, GK rats showed similar cortical S1P concentration despite higher S1P levels in plasma, yet lower density of S1PR1, S1PR2 and S1PR4 in nerve-terminal-enriched membranes. HFD-fed mice exhibited increased plasma and cortical concentrations of S1P, and decreased density of S1PR1 and S1PR4. These findings point towards altered S1P signaling in synapses of insulin resistance and diet-induced obesity models, suggesting a role of S1P signaling in T2D-associated synaptic dysfunction.show moreshow less

Download full text files

Export metadata

Statistics

Number of document requests

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Cecilia Skoug, Hüseyin Erdogan, Lotte VanherleGND, João P. P. Vieira, Frank MatthesORCiDGND, Lena Eliasson, Anja MeissnerORCiDGND, João M. N. Duarte
URN:urn:nbn:de:bvb:384-opus4-1094148
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/109414
ISSN:0364-3190OPAC
ISSN:1573-6903OPAC
Parent Title (English):Neurochemical Research
Publisher:Springer Science and Business Media LLC
Type:Article
Language:English
Year of first Publication:2023
Publishing Institution:Universität Augsburg
Release Date:2023/11/23
Tag:Cellular and Molecular Neuroscience; General Medicine; Biochemistry
Volume:49
First Page:338
Last Page:347
DOI:https://doi.org/10.1007/s11064-023-04033-4
Institutes:Medizinische Fakultät
Medizinische Fakultät / Professur für Physiologie (Meissner)
Nachhaltigkeitsziele
Nachhaltigkeitsziele / Ziel 3 - Gesundheit und Wohlergehen
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)