title: β₂-adrenergic receptors protect axons during energetic stress but do not influence basal glio-axonal lactate shuttling in mouse white matter.
abstract: In vitro studies have demonstrated that β2-adrenergic receptor activation stimulates glycogen degradation in astrocytes, generating lactate as a potential energy source for neurons. Using in vivo microdialysis in mouse cerebellar white matter we demonstrate continuous axonal lactate uptake and glial-axonal metabolic coupling of glutamate/lactate exchange. However, this physiological lactate production was not influenced by activation (clenbuterol) or blocking (ICI 118551) of β2-adrenergic receptors. In two-photon imaging experiments on ex vivo mouse corpus callosum subjected to aglycemia, β2-adrenergic activation rescued axons, whereas inhibition of axonal lactate uptake by α-cyano-4-hydroxycinnamic acid (4-CIN) was associated with severe axonal loss. Our results suggest that axonal protective effects of glial β2-adrenergic receptor activation are not mediated by enhanced lactate production.
authors: Department of Neurology, University Hospital Brussels, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Electronic address: laureysg@hotmail.com.
authors: G
authors: G
authors: Laureys
authors: Department of Physiology and Biochemistry, Faculty of Medicine & Surgery, University of Malta, Msida MSD 2080, Malta.
authors: M
authors: M
authors: Valentino
authors: Department of Neurology, University Hospital Brussels, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors: F
authors: F
authors: Demol
authors: Department of Anatomy, Faculty of Medicine & Surgery, University of Malta, Msida MSD 2080, Malta.
authors: C
authors: C
authors: Zammit
authors: Department of Physiology and Biochemistry, Faculty of Medicine & Surgery, University of Malta, Msida MSD 2080, Malta.
authors: R
authors: R
authors: Muscat
authors: Department of Neurology, University Hospital Brussels, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors: M
authors: M
authors: Cambron
authors: Experimental Pharmacology, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors: R
authors: R
authors: Kooijman
authors: Department of Neurology, University Hospital Brussels, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium; Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
authors: J
authors: J
authors: De Keyser
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D066127:White Matter / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D002491:Central Nervous System Agents; D003373:Coumaric Acids; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C007175:alpha-cyano-4-hydroxycinnamate; D019344:Lactic Acid; D018698:Glutamic Acid; C026777:ICI 118551; D002976:Clenbuterol
keywords: axons; glucose; glutamate; lactate; white matter; β2-adrenergic receptors