Restoration of (nor)adrenergic-like Ca2+ signalling counteracts age-related motor decline
- 11) Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Slovenia; 2) Laborato
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 (Tyr1R). Selective Tyr1R overexpression in (nor)adrenergic-like Tdc2 neurons prolonged lifespan, restored Ca2+ signalling and improved locomotor performance. These findings identify Tyr1R-dependent Ca2+ signalling as an age-sensitive regulator of brain metabolism and motor function.
Related
- Defective HIRA driven chromatin maintenance underlies age related decline in oocyte quality
- Integrative Multi-Omics Analysis Reveals Molecular Signatures of Age-Related Decline in Vervet Leg Skeletal Muscle
- Personality and dominance shape core area use and territory-related signalling in a feral ungulate
- An age-related decline in human fluid intelligence corresponds with immature astroglia prevalence
- Age-related decline in directed forgetting: a meta-analytic test of inhibition versus cognitive load accounts.
BibTeX
@misc{horvat2026restoration,
title = {{Restoration of (nor)adrenergic-like Ca2+ signalling counteracts age-related motor decline}},
author = {A. Horvat and U. Cerne and A.-K. Dahse and L.-S. Brodmerkel and A. Bratanic and M. Matz-Soja and S. Schirmeier and R. Zorec and N. Scholz and N. Vardjan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.754926},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.754926v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Restoration of (nor)adrenergic-like Ca2+ signalling counteracts age-related motor decline
AU - A. Horvat
AU - U. Cerne
AU - A.-K. Dahse
AU - L.-S. Brodmerkel
AU - A. Bratanic
AU - M. Matz-Soja
AU - S. Schirmeier
AU - R. Zorec
AU - N. Scholz
AU - N. Vardjan
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.754926
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.754926v1
AB - 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 (Tyr1R). Selective Tyr1R overexpression in (nor)adrenergic-like Tdc2 neurons prolonged lifespan, restored Ca2+ signalling and improved locomotor performance. These findings identify Tyr1R-dependent Ca2+ signalling as an age-sensitive regulator of brain metabolism and motor function.
ER -