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Disruption of Striatal-Enriched Protein Tyrosine Phosphatase Signaling Might Contribute to Memory Impairment in a Mouse Model of Sepsis-Associated Encephalopathy

  • Man-man Zong
  • Hong-mei Yuan
  • Xue He
  • Zhi-qiang Zhou
  • Xiao-dong Qiu
  • Jian-jun YangEmail author
  • Mu-huo JiEmail author
Original Paper
  • 9 Downloads

Abstract

Sepsis-associated encephalopathy (SAE) is a potentially irreversible acute cognitive dysfunction with unclear mechanism. Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase which normally opposes synaptic strengthening by regulating key signaling molecules involved in synaptic plasticity and neuronal function. Thus, we hypothesized that abnormal STEP signaling pathway was involved in sepsis-induced cognitive impairment evoked by lipopolysaccharides (LPS) injection. The levels of STEP, phosphorylation of GluN2B (pGluN2B), the kinases extracellular signal-regulated kinase 1/2 (pERK), cAMP-response element binding protein (CREB), synaptophysin, brain derived neurotrophic factor (BDNF), and post-synaptic density protein 95 (PSD95) in the hippocampus, prefrontal cortex, and striatum were determined at the indicated time points. In the present study, we found that STEP levels were significantly increased in the hippocampus, prefrontal cortex, and striatum following LPS injection, which might resulted from the disruption of the ubiquitin–proteasome system. Notably, a STEP inhibitor TC-2153 treatment alleviated sepsis-induced memory impairment by increasing phosphorylation of GluN2B and ERK1/2, CREB/BDNF, and PSD95. In summary, our results support the key role of STEP in sepsis-induced memory impairment in a mouse model of SAE, whereas inhibition of STEP may provide a novel therapeutic approach for this disorder and possible other neurodegenerative diseases.

Keywords

Striatal-enriched protein tyrosine phosphatase LPS Cognition Synaptic plasticity 

Notes

Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81571083, 81771156, 81772126).

Compliance with Ethical Standards

Conflict of interest

We declare that we have no competing interests.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology, Jinling Hospital, School of MedicineNanjing UniversityNanjingChina
  2. 2.Department of AnesthesiologyObstetrics and Gynecology Hospital Affiliated to Nanjing Medical UniversityNanjingChina
  3. 3.Department of Anesthesiology, Zhongda Hospital, School of MedicineSoutheast UniversityNanjingChina
  4. 4.Department of AnesthesiologyFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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