Details

Autor(en) / Beteiligte

• Li, Yanan
• Zhang, Qi
• Wang, Xupeng
• Xu, Fang
• Niu, Junfang
• Zhao, Juan
• Wang, Qiujun

Titel

IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region

Ist Teil von

• Brain research bulletin, 2024-03, Vol.208, p.110890-110890, Article 110890

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cognitive impairment is a major complication of cerebral ischemia–reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role of interleukin 17 A (IL-17A) on CIR injury-induced cognitive impairment in wild-type and IL-17A knockout mice using RNA sequencing analysis, neurological assessments, Golgi–Cox staining, dendritic spine analysis, immunofluorescence assay, and western blot analysis. RNA sequencing identified 195 CIR-induced differentially expressed genes (83 upregulated and 112 downregulated), highlighting several enriched biological processes (negative regulation of phosphorylation, transcription regulator complex, and receptor ligand activity) and signaling pathways (mitogen-activated protein kinase [MAPK], tumor necrosis factor, and IL-17 signaling pathways). We also injected adeno-associated virus into the bilateral hippocampal CA1 regions of CIR mice to upregulate or downregulate cyclic AMP response element-binding protein. IL-17A knockout activated the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and further improved synaptic plasticity, structure, and function in CIR mice. Together, our findings suggest that IL-17A deficiency alleviates CIR injury by activating the ERK/MAPK signaling pathway and enhancing hippocampal synaptic plasticity. •IL-17A is up-regulated, “IL-17 signaling pathway” and “MAPK signaling pathway” are enriched in RNA sequencing of CIR mice.•IL-17A KO ameliorates synaptic plasticity in the hippocampal CA1 region in mice with CIR injury.•IL-17A KO activates ERK/MAPK pathway in hippocampal CA1 neurons to exert a neuroprotective effect in mice with CIR injury.•Inhibition of the ERK/MAPK pathway blocks the neuroprotective effect of IL-17A KO.