The most common clinical manifestation of sepsis-related encephalopathy (SAE) is the deterioration of cognitive function. Besides, increasing evidence shows that SAE patients exhibit coordination and sensorimotor dysfunctions, suggesting that SAE affects motor function with unclear mechanism. In the present work, we explored the effects of SAE on cerebellar Purkinje cells (PCs) using cecal ligation and perforation (CLP), a standard model for inducing sepsis symptoms similar to those in human patients. Our results show that the sepsis can activate microglia in the cerebellum and promote the secretion of inflammatory factor TNF-α, which increases intrinsic excitability and synaptic transmission of PCs, inhibits the synaptic plasticity of PCs, and impairs motor learning of mice. These findings address how SAE changes PC functions, and thereby are of great significance to reveal pathophysiological feathers of human patients suffering from SAE.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
Artificial cerebrospinal fluid
Cecal ligation and perforation
Central nervous system
Colony-stimulating factor 1 receptor
Excitatory postsynaptic current
Functional magnetic resonance imaging
Miniature excitatory postsynaptic currents
Tumor necrosis factor
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This work was supported by the grant from the National Natural Science Foundation of China (81971874 to LDS).
All animal experiments were carried out in strict compliance with protocols approved by the Animal Care and Use Committee at Zhejiang University School of Medicine.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Zhao, Y., Jiang, Y., Shen, Y. et al. Sepsis Impairs Purkinje Cell Functions and Motor Behaviors Through Microglia Activation. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01531-7