Dual Role for Astroglial Copper-Assisted Polyamine Metabolism during Intense Network Activity

Astrocytes serve essential roles in human brain function and diseases. Growing evidence indicates that astrocytes are central players of the feedback modulation excitatory Glu signalling during epileptiform activity via Glu-GABA exchange. The underlying mechanism results increase tonic inhibition by reverse operation astroglial GABA transporter, induced Glu-Na+ symport. GABA, released from astrocytes, is synthesized polyamine (PA) putrescine this process involves copper amino oxidase. Through pathway, can be considered as an important source inhibitory signaling counterbalances epileptic discharges. Putrescine, however, also a precursor for spermine known to enhance gap junction channel communication and, consequently, supports long-range Ca2+ contributes spreading through astrocytic syncytium. Recently, we presented possibility neuron-glia redox coupling (Cu+/Cu2+) oxidative catabolism. In current work, explore whether Cu+/Cu2+ homeostasis involved control on neuronal excitability regulating PA We provide supporting experimental data hypothesis. show blockade transporter (CTR1) AgNO3 (3.6 µM) prevents transporter-mediated currents, indicating causal relationship between uptake catabolism astrocytes. addition, MnCl2 (20 μM), inhibitor divalent metal DMT1, Furthermore, observed facilitation added CuCl2 (2 boosts currents. These findings corroborate hypothesis drives → transformation, which leads subsequent exchange inhibition. Findings may turn highlight potential role fine-tuning tripartite synapse.