Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients

Gos, Tomasz; Myint, Aye-Mu; Schiltz, Kolja; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Busse, Stefan; Müller, Ulf; Mawrin, Christian; Bernstein, Hans‐Gert; Bogerts, Bernhard; Steiner, Johann

doi:10.1016/j.bbi.2014.05.012

Cited by 42 publications

(30 citation statements)

References 37 publications

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“…Considering the neuroinflammation hypothesis, microglial activation has been shown in vivo in schizophrenia and the possible relevance of microglia in the pathophysiology of schizophrenia is increasingly recognized . Microglia play a role in controlling a T. gondii infection in the brain , possibly through the kynurenine pathway , whereby differences of the microglial immune response to different strains of T. gondii have been found .…”

Section: Discussionmentioning

confidence: 99%

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis

Sutterland

Fond

Kuin

et al. 2015

Acta Psychiatr Scand

376

313

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Section: Discussionmentioning

confidence: 99%

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis

Sutterland

Fond

Kuin

et al. 2015

Acta Psychiatr Scand

376

313

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“…Autopsy studies have shown that the mRNA levels of GABAergic markers, glutamate decarboxylase 1 (GAD67) and parvalbumin (PV), were down-regulated in SZ patients [8,9]. Moreover, dysfunction of N-methyl-D-aspartate (NMDA) receptor, which is mainly expressed in GABAergic neurons, might also play a role in SZ development [10], and NMDA receptor antagonists mimic schizophrenia-like symptoms in mice [11]. MK801 (dizocilpine), a potent non-competitive NMDA receptor antagonist, is widely used to induce schizophrenia in animal models.…”

Section: Introductionmentioning

confidence: 98%

Sub-chronic Antipsychotic Drug Administration Reverses the Expression of Neuregulin 1 and ErbB4 in a Cultured MK801-Induced Mouse Primary Hippocampal Neuron or a Neurodevelopmental Schizophrenia Model

Tang

Yang

et al. 2016

Neurochem Res

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It has been reported that specific environmental influences during the postpartum period might contribute to the development of schizophrenia (SZ). Administration of MK801 during early development led to persistent brain pathology. Glutamate decarboxylase 1 (GAD67) and parvalbumin (PV), and neuregulin 1 (NRG1)/ErbB4 signaling were closely associated with SZ pathology. We postulated therefore that NMDA receptor antagonists exposure during the postpartum period may be associated with expression dysregulation of some of the SZ candidate proteins. To test this, we used mouse primary hippocampal neurons and neonatal male mice treated with the NMDA receptor antagonist, MK801 at postnatal day 4 (P4) or P7, followed by the treatments of antipsychotic drugs (i.e., olanzapine, risperidone, and haloperidol). The expressions of GAD67, PV, NRG1, and ErbB4 in in vitro and in vivo SZ models were detected with Western blot analysis and immunohistochemistry, respectively. Behavioral tests (locomotion activity, social interaction, novel object recognition and prepulse inhibition) were measured. We found MK801 decreased the expression of GAD67, PV, NRG1 and ErbB4, and induced obvious behavioral alterations, while antipsychotics reversed these alterations. These results suggest that exposure to the NMDA receptor antagonist in early development may lead to long-lasting influence on the expression of specific proteins, such as GAD67, PV, NRG1, and ErbB4. Moreover, our results suggest that rescue of the activation of the NRG1/ErbB4 signaling pathway may be one of the mechanisms by which antipsychotic drugs have an antipsychotic effect.

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“…Additionally, there were significantly more QUIN-immunoreactive microglial cells in the CA1 hippocampal subregions of schizophrenia patients. However, no significant changes in quinolinic acid (QUIN)-immunoreactive microglial cells were observed in the hippocampus CA2/3 and dentate gyrus regions of patients with schizophrenia [36].…”

Section: Schizophreniamentioning

confidence: 99%

“…A significant increase was observed in the mean protein CD11b levels in the frontal cortex of patients with schizophrenia compared with controls [27]. CD11b is one of the most important phagocyte receptors for recognizing microbial pathogens [35], and it has been found in murine [36,37] and human microglia [38]; furthermore, it is widely used as a marker for microglial identification. A qualitative assessment of IBA-1-stained microglial morphology demonstrated numerous activated microglial cells in the dorsolateral prefrontal cortex of schizophrenia patients [32].…”

Section: Schizophreniamentioning

confidence: 99%

“…There were no statistically significant changes in the numbers of HLA-DR-positive cells in the anterior cingulate cortex [30,[33][34][35], dorsolateral prefrontal cortex [28,33,34], hippocampus [31,33,34,36], mediodorsal thalamus [33,34] and dentate gyrus [34] from patients with schizophrenia. CD68-positive microglia were not altered in the mediodorsal thalamus [37] and dorsolateral prefrontal cortex [38] in patients with schizophrenia.…”

Section: Schizophreniamentioning

confidence: 99%

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Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

Sakai

Takahashi

et al. 2016

NIB

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Abstract.As recent studies have shown that microglia play a key role in inflammation and immunological challenges as well as have broader roles in synaptic modulation in the brain, studies on psychiatric disorders have increasingly focused on microglia. Microglial abnormalities have consistently been observed in psychiatric postmortem brain studies, including altered microglial activation and changes in the protein and mRNA expression levels of microglial marker molecules, such as major histocompatibility complex, class II, DR (HLA-DR), complement receptor type 3 (CD11b), ionized calcium binding adaptor molecule 1 (IBA-1), macrosialin (CD68) and glucose transporter type 5 (GLUT5). Microglial abnormalities have also been observed in positron emission tomography (PET) studies. Recent advances in omics-based microglial gene expression profiling of psychiatric brains may elucidate microglial involvement in the pathogeneses of psychiatric disorders. In the present paper, we review the current status of research on expression profiling of microglia-relevant molecules in psychiatric postmortem and imaging studies and we discuss future research directions.

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Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients

Cited by 42 publications

References 37 publications

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis

Sub-chronic Antipsychotic Drug Administration Reverses the Expression of Neuregulin 1 and ErbB4 in a Cultured MK801-Induced Mouse Primary Hippocampal Neuron or a Neurodevelopmental Schizophrenia Model

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

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