Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Abstract

BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0688-2) contains supplementary material, which is available to authorized users.

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

“…The results of this study indicating that both microglia and astrocytes are significantly activated in the hippocampus of Gunn rats as shown by immunohistochemistry using Iba1 and S100B are consistent with our previous studies which demonstrated increased immunoreactivity for another microglial marker CD11b (Furuya et al., 2013; Liaury et al., 2012, 2014) and for another astrocytic marker GFAP (Limoa et al., 2016) in the hippocampal DG, CA1, and CA3. These observations of the increased immunoreactivity using two distinct markers for each glial cell substantiate both microglial activation and astrocytic activation in the hippocampus of Gunn rats.…”

“…Therefore, Gunn rats have been used as an experimental model of kernicterus (bilirubin encephalopathy), which can be considered as an organic brain disorder. As patients with organic brain disorder often present symptoms of schizophrenia and affective disorder (Hamilton, Frick, Takahashi, & Hopping, 1983), it is not unexpected that Gunn rats show depression‐like behavior as demonstrated by this study and schizophrenia‐like behavior as shown by our previous studies (Furuya et al., 2013; Liaury et al., 2012, 2014; Limoa et al., 2016). It has been shown that a neuronal damage in the hippocampus is caused by unconjugated bilirubin in growing Gunn rats (Ohno, 1981).…”

“…We modified and followed the immunohistochemical procedure described in our previous study (Limoa et al., 2016). The free‐floating brain sections were incubated in 1% H 2 O 2 for 30 min at RT and then were preincubated with 0.1 M PB containing 3% bovine serum albumin, 0.2% Triton X and 1.5% goat serum for 1 hr at RT.…”

“…However, the numbers of established models which show signs or symptoms relevant to the diseases are limited. We previously demonstrated that Gunn rats with hyperbilirubinemia showed the activation of both microglia stained with CD11b (Furuya et al., 2013; Liaury et al., 2012, 2014; Limoa et al., 2016) and astrocytes stained with glial fibrillar acidic protein (GFAP) (Limoa et al., 2016) in the hippocampus and exhibited schizophrenia‐like behavior in the prepulse inhibition test (Liaury et al., 2014; Limoa et al., 2016), the object‐location test (Furuya et al., 2013), and the novel object recognition test (Liaury et al., 2014). …”

Association study of GFAP Polymorphisms with schizophrenia in Han Chinese population

“…This suggests that there is a specific glial cell type change in SCZ. A recent animal study found a significant increase of GFAP in the hippocampus of Gunn rats with schizophrenic-like behavior [9] . Sun et al (2017) first observed a significant increase in GFAP in models involving socially isolated animals [10] .…”