Whole brain irradiation in mice causes long-term impairment in astrocytic calcium signaling but preserves astrocyte-astrocyte coupling.

摘要: Whole brain irradiation (WBI) therapy is an important treatment for metastases and potential microscopic malignancies. WBI promotes progressive cognitive dysfunction in over half of surviving patients, yet, the underlying mechanisms remain obscure. Astrocytes play critical roles regulation neuronal activity, metabolism, cerebral blood flow, while neurons are considered radioresistant, astrocytes sensitive to γ-irradiation. Hallmarks astrocyte function ability generate stimulus-induced intercellular Ca2+ signals move metabolic substrates through connected network. We tested hypothesis that WBI-induced impairment associates with persistent astrocytic signaling and/or gap junctional coupling. Mice were subjected a clinically relevant protocol fractionated WBI, 12 15 months after irradiation, we confirmed compared controls. To test integrity astrocyte-to-astrocyte coupling postWBI, loaded Alexa-488-hydrazide by patch-based dye infusion, increase fluorescence signal neighboring cell bodies was assessed 2-photon microscopy acute slices sensory-motor cortex. found did not affect Astrocytic responses induced bath administration phenylephrine (detected Rhod-2/AM) also unaltered WBI. However, electrical stimulation used long-term potentiation (theta burst), revealed attenuated arbor soma Our data show causes long-lasting decrement synaptic-evoked 12-15 postirradiation, which may be contributor decline seen