Journal
NEUROPHARMACOLOGY
Volume 217, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2022.109191
Keywords
Postoperative delirium; Hippocampus; Astrocytes; Cholinergic inputs; Synaptic plasticity; Cognitive function
Categories
Funding
- Natural Science Foundation of Xinjiang, China [2020D01C212]
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Postoperative delirium is a serious health problem occurring after major surgery. The study found that malfunctioned astrocytes in the hippocampus contribute to cognitive dysfunction in postoperative delirium. The study suggests that targeting astrocyte activation and acetylcholine receptors may be a valuable strategy for intervention.
Postoperative delirium (POD) occurs in a few days after major surgery under general anesthesia and may cause serious health problems. However, effective intervention and treatment remain unavailable because the underlying mechanisms have far been elucidated. In the present study, we explored the role of the malfunctioned astrocytes in POD. Our results showed that mice with tibia fracture displayed spatial and temporal memory impairments, reduced LTP, and activated astrocytes in the hippocampus in early postoperative stage. Using electrophysiological and Ca2+ imaging techniques in hippocampal slices, we demonstrated the malfunctions of astrocytes in surgery mice: depolarized resting membrane potential, higher membrane conductance and capacitance, and attenuated Ca2+ elevation in response to external stimulation. The degraded calcium signaling in hippocampal astrocytes in surgery mice was restored by correcting the diminution of acetylcholine release with galantamine. Furthermore, pharmacologically blocking astrocyte activation with fluorocitrate and enhancing cholinergic inputs with galantamine normalized hippocampal LTP in surgery mice. Finally, inhibition of astrocyte activation with fluorocitrate in the hippocampus improved cognitive function in surgery mice. Therefore, the prevention of astrocyte activation may be a valuable strategy for the intervention of cognitive dysfunction in POD, and acetylcholine receptors may be valid drug targets for this purpose.
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