S100B+ Astrocytes Are Altered in the Mouse Brain Upon Ketamine Challenge: Implications for the Symptoms of Schizophrenia.

Ketamine, an NMDA receptor antagonist used to model schizophrenia in mice, causes changes in S100B+ astrocytes in the brain. Mice given ketamine for 10 days showed astrocyte activation and morphological shifts from ramified to amoeboid forms in the cerebral cortex and olfactory lobes, along with increased numbers of S100B+ astrocytes in those regions. The hippocampus showed activation but no increase in astrocyte number. In cultured LN229 glial cells, ketamine increased S100B expression. These findings link astrocyte alterations to schizophrenia symptoms.

Study at a glance

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by positive, negative and cognitive symptoms. The pathophysiology of schizophrenia is largely unknown, but it is understood that this mental disorder is a manifestation of genetic, environmental and biological factors. Herein, we focus on S100B, a family of calcium binding cytosolic proteins that play a profound role in glial proliferation, differentiation and maintenance. S100B is also related to the pathology and its increased level can be seen in the serum of individuals with schizophrenia, where it is associated with neuroinflammation and neuronal injury. Ketamine, a dissociative anesthetic and NMDA receptor antagonist, is widely used to model schizophrenia-like behaviors in mice. Using this model, we studied the changes in expression of S100B+ astrocytes in cerebrum, hippocampus and olfactory lobe. Swiss albino mice administered with ketamine (100 mg/kg) for 10 consecutive days exhibited significant morphological alterations in astrocytes in cerebral cortex, hippocampus and olfactory lobes. The cerebral cortex and olfactory lobes were most vulnerable to ketamine. In these regions, S100B+ astrocytes shifted their morphology from ramified to amoeboid form indicating gliosis. These regions also demonstrated a high population of S100B+ astrocytes. The hippocampal region only showed astrocyte activation without change in number of S100B+ astrocytes. In vitro, LN229 glial cells when challenged with ketamine exhibited increased cellular expression of S100B by immunoblotting. Together it can be concluded that ketamine induced schizophrenia increases cellular expression of S100B and induces astrocyte activation. This study underpins alterations in S100B+ astrocytes as an implication for symptom of schizophrenia.