Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction.

Zuo Zhang,Jiyin Zhou,Hongli Zhou

doi:10.1530/jme-20-0321

Abstract

Earlier, it was shown that reversing the downregulation of neuritin expression in the brain improves central neuropathy in diabetic rats. We investigated the protective mechanism of neuritin in diabetic cognitive dysfunction via astrocytes. Further, the impact of the overexpression of neuritin in the cortex and the hippocampus on diabetic cognitive dysfunction and astrogliosis in type 2 diabetic (db/db) mice was assessed. Antagonists were used to inhibit the JAK2/STAT3 signaling pathway in U-118MG, an astrocyte cell line. Immunofluorescence, Western blotting, and real-time PCR were performed. Neuritin overexpression in the hippocampus of db/db mice significantly ameliorated cognitive dysfunction, hippocampal neuronal impairment, and synaptic plasticity deterioration, and inhibited astrogliosis and the JAK2/STAT3 signaling pathway in the hippocampus. Neuritin suppressed the JAK2/STAT3 signaling pathway to inhibit lipopolysaccharide-induced gliosis in U-118MG cells. It was observed that neuritin regulates the JAK2/STAT3 signaling pathway in astrocytes to inhibit astrogliosis and improve diabetic cognitive dysfunction.

Highlights

The incidence of cognitive dysfunction in patients with type 2 diabetes is 1.5 times higher than that in nondiabetic patients and 60 to 70% of diabetes patients have cognitive dysfunction
We employed the overexpression of neuritin in the cortex and hippocampus of type 2 diabetic mice and lipopolysaccharide induction of U-118MG astrocyte cell line to investigate the effects of neuritin on diabetic cognitive dysfunction and astrogliosis through the JAK2/STAT3 signaling pathway
Our study found that neuritin overexpression in the hippocampus of db/db mice significantly ameliorated cognitive dysfunction, neuronal impairment, and synaptic plasticity, and inhibited astrogliosis and the JAK2/STAT3 signaling pathway in the hippocampus

Summary

Introduction

The incidence of cognitive dysfunction in patients with type 2 diabetes is 1.5 times higher than that in nondiabetic patients and 60 to 70% of diabetes patients have cognitive dysfunction. Diabetic rats display astrogliosis in the cortex and hippocampus (Tomassoni et al 2013); while type 2 diabetic mice show synaptic dysfunction and astrogliosis with memory impairment (Duarte et al 2012). The JAK2/STAT3 signaling pathway has emerged as a central regulator of astrocyte reactivity and plays a critical role in animal models that regulate synaptic plasticity, reactive gliosis, and cognitive dysfunction (Ceyzeriat et al 2016). We employed the overexpression of neuritin in the cortex and hippocampus of type 2 diabetic (db/db) mice and lipopolysaccharide induction of U-118MG astrocyte cell line to investigate the effects of neuritin on diabetic cognitive dysfunction and astrogliosis through the JAK2/STAT3 signaling pathway.

Result

Findings

Discussion