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Sepsis Impairs Purkinje Cell Functions and Motor Behaviors Through Microglia Activation

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A Correction to this article was published on 24 February 2023

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Abstract

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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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Change history

Abbreviations

aCSF:

Artificial cerebrospinal fluid

BBB:

Blood-brain barrier

CF:

Climbing fiber

CLP:

Cecal ligation and perforation

CNS:

Central nervous system

CSF1R:

Colony-stimulating factor 1 receptor

EPSC:

Excitatory postsynaptic current

fMRI:

Functional magnetic resonance imaging

GABA:

γ-Aminobutyric acid

LTD:

Long-term depression

LTP:

Long-term potentiation

mEPSCs:

Miniature excitatory postsynaptic currents

OKR:

Optokinetic reflex

PC:

Purkinje cell

PF:

Parallel fiber

PPF:

Paired-pulse facilitation

RT:

Room temperature

SAE:

Sepsis-related encephalopathy

TNF-α:

Tumor necrosis factor

VOR:

Vestibulo-ocular reflex

VVOR:

Visually-enhanced VOR

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Funding

This work was supported by the grant from the National Natural Science Foundation of China (81971874 to LDS).

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Authors and Affiliations

  1. Department of Physiology and Neuroscience Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China

    Yue Zhao, Yao Jiang, Ying Shen & Li-Da Su

  2. Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, 310009, China

    Li-Da Su

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  1. Yue Zhao
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Contributions

Y.S. and L.-D.S. wrote the main manuscript text and Y.Z. and J.Y. prepared Figs. 1–4. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Ying Shen or Li-Da Su.

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Ethical Approval

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.

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The authors declare no competing interests.

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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

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