20.500.12556/RUL-183556 Dopamine-induced L-lactate production in cortical astrocytes cross-reacts with β1-adrenoceptor-mediated cAMP signalling Astrocytes maintain homeostasis of the central nervous system and supply neurons with metabolic substrates essential for synaptic plasticity and learning. Upon stimulation by noradrenaline (NA), released primarily by locus coeruleus (LC) neurons and acting via volume transmission, astrocytes enhance aerobic glycolysis and produce L-lactate, a process critical for energy support yet dependent on β-adrenoceptor– mediated cyclic adenosine monophosphate (cAMP) signalling. In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, early degeneration of the LC diminishes noradrenergic tone, potentially impairing astrocyte metabolic function. Dopamine (DA), acting via volume transmission like NA, released from the substantia nigra pars compacta, may also modulate astrocytic metabolism; however, this has not yet been investigated at the cellular level. Using fluorescence resonance energy transfer-based nanosensor imaging in cultured rat cortical astrocytes, we investigated DA-induced cAMP signalling and L-lactate production. DA elicited a dose-dependent increase in cytosolic cAMP (EC50 = 1.25 μM) and stimulated delayed L-lactate production in a receptor-mediated, cAMP-dependent manner. Knockdown of β₁-adrenoceptors (Adrb1) significantly reduced these effects. At the same time, super-resolution stimulated emission depletion microscopy revealed minimal nanoscale colocalization between D1 and β₁ receptors, suggesting that at least at higher DA concentrations, β₁-adrenoceptors contribute to DA-mediated metabolic regulation. These findings identify a novel dopaminergic pathway for astrocytic glycolytic activation, informing future studies examining dysregulation of monoaminergic–astrocytic signalling in neurodegenerative diseases. astrocytes dopamine volumen transmitter cyclic AMP L-lactate energy metabolism astrociti dopamin volumski transmiter ciklični AMP L-laktat energijski metabolizem true false true Angleški jezik Slovenski jezik Članek v reviji 2026-06-15 08:59:20 2026-06-15 08:59:28 2026-07-23 07:41:32 0000-00-00 00:00:00 2026 0 0 16 str. iss. 3 Vol. 18 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 2152-5250 10.14336/AD.2025.1442 275352323 RAZ_Sugiyama_Keita_2026.pdf RAZ_Sugiyama_Keita_2026.pdf 1 BFCC2A6335EAAB4FA73542E0E989B267 a432b5be191f287a0fbdf153a736097879650b5d5358d5a3e21efb69b23ae5ae 1189343a-7943-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=237188 https://www.aginganddisease.org/EN/10.14336/AD.2025.1442 1 b862de28-6887-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=235618 Medicinska fakulteta 0 0 0