LncRNA Neat1 Regulates Neuronal Dysfunction Post-sepsis Via Stabilization of Hemoglobin Subunit Beta

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2022 Mar 25

PMID 35331906

Authors

Yan Wu

Pengfei Li

Liu Liu

Andrew J Goodwin

Perry V Halushka

Tetsuro Hirose

Shinichi Nakagawa

Jiliang Zhou

Meng Liu

Hongkuan Fan

Affiliations

Soon will be listed here.

Abstract

Sepsis-associated encephalopathy (SAE) is characterized by acute and diffuse brain dysfunction and correlates with long-term cognitive impairments with no targeted therapy. We used a mouse model of sepsis-related cognitive impairment to examine the role of lncRNA nuclear enriched abundant transcript 1 (Neat1) in SAE. We observed that Neat1 expression was increased in neuronal cells from septic mice and that it directly interacts with hemoglobin subunit beta (Hbb), preventing its degradation. The Neat1/Hbb axis suppressed postsynaptic density protein 95 (PSD-95) levels and decreased dendritic spine density. Neat1 knockout mice exhibited decreased Hbb levels, which resulted in increased PSD-95 levels, increased neuronal dendritic spine density, and decreased anxiety and memory impairment. Neat1 silencing via the antisense oligonucleotide GapmeR ameliorated anxiety-like behavior and cognitive impairment post-sepsis. In conclusion, we uncovered a previously unknown mechanism of the Neat1/Hbb axis in regulating neuronal dysfunction, which may lead to a novel treatment strategy for SAE.

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