The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

ludc web

Joao Duarte

Research team manager

ludc web

Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture

Author

  • Cecilia Skoug
  • Isak Martinsson
  • Gunnar K Gouras
  • Anja Meissner
  • João M N Duarte

Summary, in English

Sphingosine-1-phosphate (S1P) is best known for its roles as vascular and immune regulator. Besides, it is also present in the central nervous system (CNS) where it can act as neuromodulator via five S1P receptors (S1PRs), and thus control neurotransmitter release. The distribution of S1PRs in the active zone and postsynaptic density of CNS synapses remains unknown. In the current study, we investigated the localization of S1PR1-5 in synapses of the mouse cortex. Cortical nerve terminals purified in a sucrose gradient were endowed with all five S1PRs. Further subcellular fractionation of cortical nerve terminals revealed S1PR2 and S1PR4 immunoreactivity in the active zone of presynaptic nerve terminals. Interestingly, only S1PR2 and S1PR3 immunoreactivity was found in the postsynaptic density. All receptors were present outside the active zone of nerve terminals. Neurons in the mouse cortex and primary neurons in culture showed immunoreactivity against all five S1PRs, and Ca 2+ imaging revealed that S1P inhibits spontaneous neuronal activity in a dose-dependent fashion. When testing selective agonists for each of the receptors, we found that only S1PR1, S1PR2 and S1PR4 control spontaneous neuronal activity. We conclude that S1PR2 and S1PR4 are located in the active zone of nerve terminals and inhibit neuronal activity. Future studies need to test whether these receptors modulate stimulation-induced neurotransmitter release.

Department/s

  • MultiPark: Multidisciplinary research focused on Parkinson´s disease
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes and Brain Function
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Experimental Dementia Research
  • Vascular Biology

Publishing year

2022-07-04

Language

English

Pages

3114-3125

Publication/Series

Neurochemical Research

Volume

47

Issue

10

Document type

Journal article

Publisher

Springer

Topic

  • Inorganic Chemistry
  • Neurosciences
  • Physiology

Status

Published

Research group

  • Diabetes and Brain Function
  • Experimental Dementia Research
  • Vascular Biology

ISBN/ISSN/Other

  • ISSN: 1573-6903