Region-specific brain area reductions and increased cholecystokinin\xa0positive neurons in diabetic OLETF rats: implication for anxiety-like behavior

Ryosuke Ochi,Naoto Fujita,Duc Trung Le,Son Tien Nguyen,Natsuki Goto,Susumu Urakawa,Hisao Nishijo,Taketoshi Ono,Kojiro Matsushita

doi:10.1186/s12576-020-00771-0

Abstract

Metabolic disorders can induce psychiatric comorbidities. Both brain and neuronal composition imbalances reportedly induce an anxiety-like phenotype. We hypothesized that alterations of localized brain areas and cholecystokinin (CCK) and parvalbumin (PV) expression could induce anxiety-like behavior in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Twenty-week-old OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used. The areas of corticolimbic regions were smaller in OLETF rats. The densities of CCK positive neurons in the lateral and basolateral amygdala, hippocampal cornu ammonis area 2, and prelimbic cortex were higher in OLETF rats. The densities of PV positive neurons were comparable between OLETF and LETO rats. Locomotion in the center zone in the open field test was lower in OLETF rats. These results suggest that imbalances of specific brain region areas and neuronal compositions in emotion-related areas increase the prevalence of anxiety-like behaviors in OLETF rats.

Highlights

Metabolic disorders, such as obesity and type 2 diabetes, induce several neurological comorbidities in the peripheral nervous system, but in the central nervous system as well
Though the areas at anterior to posterior (AP) − 0.12 and − 4.56 mm from the bregma were comparable between Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, the areas of whole sections at AP 2.76 and 2.28 mm from the bregma were significantly smaller in OLETF rats than in LETO rats
The main findings of this study showed that OLETF rats exhibited decreased brain weight and area, especially in the forebrain, and increased CCK levels and unchanged PV positive neuron numbers in the corticolimbic system in the early stage of type 2 diabetes; further, OLETF rats exhibited increased anxiety-like behavior in the open field test

Summary

Introduction

Metabolic disorders, such as obesity and type 2 diabetes, induce several neurological comorbidities in the peripheral nervous system, but in the central nervous system as well. Psychiatric disorders such as cognitive impairment, depression, and anxiety are attracting considerable attention [1, 2]. Psychiatric disorders, cognitive impairment and anxiety, are found to be induced by type 2 diabetes, but by obesity and metabolic syndrome as well [3, 4]. Anxiety in type 2 diabetes may be associated with imbalances in brain morphology and histology

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