Year: 2026
Type: preprint
Abstract: Aging disrupts neural function, but whether impaired noradrenergic control of brain metabolism contributes to functional decline remains unclear. Using genetically encoded fluorescent sensors we measured metabolic and signaling responses in neurons and glia of living Drosophila brains following stimulation with octopamine, the invertebrate analogue of noradrenaline. Aging was accompanied by neurodegeneration, reduced locomotion and enhanced oxidative whole-brain metabolism. Octopamine increased D-glucose uptake selectively in astrocytes and elevated L-lactate in both astrocytes and neurons, consistent with astrocytic glycolysis coupled to neuronal L-lactate uptake; monocarboxylate transporter inhibition caused selective astrocytic L-lactate accumulation. In aged animals octopamine-evoked metabolic responses in astrocytes and neural Ca²⁺ transients were markedly reduced. This impairment was associated with lower expression of adrenoceptor-like tyramine 1 receptor (Tyr 1 R). Selective Tyr 1 R overexpression in (nor)adrenergic-like Tdc2 neurons prolonged lifespan, restored Ca²⁺ signalling and improved locomotor performance. These findings identify Tyr 1 R-dependent Ca²⁺ signalling as an age-sensitive regulator of brain metabolism and motor function.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W7220385998