• Br J Anaesth · Sep 2023

    Reducing complement activation during sleep deprivation yields cognitive improvement by dexmedetomidine.

    • Qian Zhai, Ying Zhang, Mao Ye, Shan Zhu, Jianyu Sun, Yue Wang, Bin Deng, Daqing Ma, and Qiang Wang.
    • Department of Anaesthesiology and Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    • Br J Anaesth. 2023 Sep 1; 131 (3): 542555542-555.

    BackgroundSleep loss and its associated conditions (e.g. cognitive deficits) represent a large societal burden, but the underlying mechanisms of these cognitive deficits remain unknown. This study assessed the effect of dexmedetomidine (DEX) on cognitive decline induced by sleep loss.MethodsC57BL/6 mice were subjected to chronic sleep restriction (CSR) for 20 h (5 pm-1 pm the next day) daily for 7 days, and cognitive tests were subsequently carried out. The neuromolecular and cellular changes that occurred in the presence and absence of DEX (100 μg kg-1, i.v., at 1 pm and 3 pm every day) were also investigated.ResultsCSR mice displayed a decline in learning and memory by 12% (P<0.05) in the Y-maze and by 18% (P<0.01) in the novel object recognition test; these changes were associated with increases in microglial activation, CD68+ microglial phagosome counts, astrocyte-derived complement C3 secretion, and microglial C3a receptor expression (all P<0.05). Synapse elimination, as indicated by a 66% decrease in synaptophysin expression (P=0.0004) and a 45% decrease in postsynaptic density protein-95 expression (P=0.0003), was associated with the occurrence of cognitive deficits. DEX activated astrocytic α2A adrenoceptors and inhibited astrocytic complement C3 release to attenuate synapse elimination through microglial phagocytosis. DEX restored synaptic connections and reversed cognitive deficits induced by CSR.ConclusionsThe results demonstrate that complement pathway activation associated with synapse elimination contributes to sleep loss-related cognitive deficits and that dexmedetomidine protects against sleep deprivation-induced complement activation. Dexmedetomidine holds potential for preventing cognitive deficits associated with sleep loss, which warrants further study.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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