Norepinephrine Couples Astrocytic Metabolism to mTOR-Driven Protein Synthesis

Abstract

Norepinephrine is a neuromodulator that regulates diverse physiological processes in the central nervous system, including astrocytic metabolism. While its metabolic actions in astrocytes are well characterised, its role in regulating protein synthesis remains unknown. Here, we show that norepinephrine robustly stimulates protein synthesis in rat primary cortical astrocytes in a time-dependent manner, comparable to that of insulin and serum. This effect is mediated predominantly by β-adrenergic receptors and is accompanied by activation of the mTOR–S6K signalling pathway. We further demonstrate that this translational response requires glycolytic activity and is preceded by a rapid depletion of astrocytic glycogen stores and a transient reduction in ATP levels. Together with growth factors, these findings identify protein synthesis as a previously unrecognised physiological target of norepinephrine in astrocytes and reveal a mechanism linking neuromodulatory signalling, metabolic state and mTOR-dependent translational control in the brain.