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 b2-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 b2-adrenergic receptors. In two-photon imaging experiments on ex vivo mouse corpus callosum

subjected to aglycemia, b2-adrenergic activation rescued axons, whereas inhibition of axonal lactate uptake by a-cyano-4-hydroxycinnamic acid (4-CIN) was associated with severe axonal loss. Our results suggest that axonal protective effects of glial b2-adrenergic receptor activation are not mediated by enhanced lactate production.