Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.

ABSTRACT: Octopamine is a well-established invertebrate neurotransmitter involved in fight or flight responses. In mammals, its function was replaced by epinephrine. Nevertheless, it is present at trace amounts and can modulate the release of monoamine neurotransmitters by a yet unidentified mechanism. Here, through a multidisciplinary approach utilizing in vitro and in vivo models of α-synucleinopathy, we uncovered an unprecedented role for octopamine in driving the conversion from toxic to neuroprotective astrocytes in the cerebral cortex by fostering aerobic glycolysis. Physiological levels of neuron-derived octopamine act on astrocytes via a trace amine-associated receptor 1-Orai1-Ca²⁺-calcineurin-mediated signaling pathway to stimulate lactate secretion. Lactate uptake in neurons via

SUBMITTER: Shum A 

PROVIDER: S-EPMC10151466 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature