Diabetic db/db mice exhibit central nervous system and peripheral molecular alterations as seen in neurological disorders

A Ernst,K M Elased,P C Guest,S Bahn,H Rahmoune,A N Sharma

doi:10.1038/tp.2013.42

Abstract

The db/db mouse is a widely used preclinical model in diabetes research. Recent studies have shown that these mice also display aspects of psychosis and depression-like behaviors as seen in some psychiatric disorders. Here, we have performed multiplex immunoassay and liquid chromatography mass spectrometry profiling of the plasma and brain samples from db/db and control mice to identify altered pathways, which could be related to these behavioral abnormalities. This is the first study to carry out profiling of the brain proteome in this model. Plasma from the db/db mice had increased levels of leptin and insulin, decreased levels of peptide YY, glucagon and prolactin and alterations in inflammation-related proteins, compared with control mice. Frontal cortex tissue from the db/db mice showed changes in proteins involved in energy metabolism, cellular structure and neural functioning, and the hippocampus had changes in proteins involved in the same pathways, with additional effects on cellular signalling proteins. The overlap of these findings with effects seen in type 2 diabetes, schizophrenia, major depressive disorder and Alzheimer's disease might contribute to a common endophenotype seen in metabolic and neurological disorders.

Highlights

The link between metabolic conditions such as diabetes and psychiatric disorders has been reported widely.[1]
The db/db mouse has been used as a model of type 2 diabetes mellitus and other metabolic conditions, such as obesity and dyslipidemia.[5]
Several other molecules were present at higher levels in the db/db mice, including insulin, C-reactive protein, serum amyloid P component, immunoglobulin A, interleukin 18, monocyte chemotactic proteins 1 and 3 and fibrinogen

Summary

Introduction

The link between metabolic conditions such as diabetes and psychiatric disorders has been reported widely.[1] In most cases, metabolic abnormalities have been identified in association with psychiatric disorders as a side effect induced by commonly prescribed anti-psychotic medications.[2] recent studies have shown that such changes can occur at disease onset even before medications have been applied. The db/db mouse has been used as a model of type 2 diabetes mellitus and other metabolic conditions, such as obesity and dyslipidemia.[5] This model was first described in 1965 by Hummel et al.,[6] who identified random mutations in mice associated with obesity and excessive hunger. The db/db mouse model mirrors the clinical picture of type 2 diabetes mellitus

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Conclusion