LncRNA Lethe protects sepsis-induced brain injury via regulating autophagy of cortical neurons

C. Mai, L. Qiu, Y. Zeng, H.-G. Jian

Department of Emergency, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. hgjian@sohu.com

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• Neurology

OBJECTIVE: To investigate the role of long non-coding RNA (lncRNA) Lethe in mediating autophagy of cortical neurons in mice with sepsis-induced brain injury (SIBI).
MATERIALS AND METHODS: A total of 60 wild-type C57BL/6 mice were divided into sham-operated wild-type (SWT) group and wild-type model (MWT) group. Sixty Lethe-/- mice were divided into sham-operated knockout (SKO) group and model knockout (MKO) group. Each group had 30 mice. Sepsis model in mice was established by cecal ligation and puncture (CLP). Neurobiological score was recorded at 6 h after CLP. Mice with lower than 6 scores of neurobehavioral tests were diagnosed with SIBI. Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to determine mRNA levels of Lethe and interferon-γ (INF-γ) in cortical neurons of SIBI mice. Western blot was conducted to detect protein levels of LC3-II, LC3-I and SQSTM1 in mice. Neuronal impairment in mouse brain was evaluated by hematoxylin and eosin (HE) staining.
RESULTS: Expressions of LC3-I and LC3-II in cerebral cortex of MWT group began to increase at 6 h after CLP, and remained at high levels until 96 h. On the contrary, SQSTM1 expression in cerebral cortex of MWT group began to decrease at 6 h after CLP. Compared with SWT group, expressions of Lethe and IFN-γ were remarkably upregulated in cortex of MWT group at 12 h after CLP. Expression of LC3-II in MWT group was remarkably upregulated, while SQSTM1 was downregulated at 12 h after CLP, which were contrary to those in MKO group. At 12 h after CLP, the neurobiological scores of the MKO group (4.97±0.71) were markedly lower than those of the MWT group (5.43±0.86). HE staining showed worse damage in cerebral cortex and fewer neurons of MKO group relative to MWT group.
CONCLUSIONS: Lethe has a protective effect on SIBI mice by regulating autophagy in mouse cortical neurons.

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