Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model

Kristian Liaury,Motohide Furuya,Masa Ieda,Toshiko Tsumori,Andi Jayalangkara Tanra,Jun Horiguchi,Michiyo Taki,Kotomi Ishihara,Keiko Tsuchie,Tsuyoshi Miyaoka,Rei Wake

doi:10.1186/1742-2094-9-56

Kristian Liaury, Motohide Furuya + Show 9 more

Open Access

https://doi.org/10.1186/1742-2094-9-56

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Abstract

BackgroundSchizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats.MethodsUsing immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus.ResultsWe found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function.ConclusionsWe propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.

Highlights

Schizophrenia is a complex and debilitating mental disorder with a prevalence of approximately 1% worldwide
Light and confocal microscopy of ionized calcium binding adaptor molecule 1 (Iba1)-labeled microglial cells We found Iba1-labeled microglial cells throughout the hilus and in the subgranular zone (SGZ), granular layer (GL), and molecular layer (ML) in the hippocampal
Our result showed no significant difference between Iba1labeled microglial cell numbers in Gunn rats and in controls

Summary

Introduction

Schizophrenia is a complex and debilitating mental disorder with a prevalence of approximately 1% worldwide. The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an N-methyl-D-aspartate (NMDA) antagonism in schizophrenia [8,9]. We suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. We examined how microglial cells respond to bilirubin toxicity in adult Gunn rats

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