Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study

Picker, Livia De; Mendez-Victoriano, Gerardo; Richards, Rhys; Gorvett, Alexander J.; Lyons, Simeon; Buckland, George R.; Tofani, Tommaso; Norman, Jeanette L.; Chatelet, David S.; Nicoll, James; Boche, Delphine

doi:10.1016/j.bbi.2021.07.017

Cited by 30 publications

(19 citation statements)

References 86 publications

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“…It is not only a marker of cell proliferation but also carries the potential to label lysosomal and endosomal transmembrane glycoproteins of microglia, indicating phagocytic activity [ 97 ]. Previous literature looking at CD68 expression in control and schizophrenia cases has reported ambiguous outcomes [ 98 , 99 ].…”

Section: Discussionmentioning

confidence: 99%

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Chamera

Curzytek

Kamińska

et al. 2022

Cells

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The maternal immune activation produced by the systemic administration of lipopolysaccharide (LPS) in rats provides valuable insights into the basis of behavioural schizophrenia-like disturbances and biochemical changes in the brains of the offspring, such as microglial activation. Regarding therapy, antipsychotics continually constitute the cornerstone of schizophrenia treatment. To their various efficacy and side effects, as well as not fully recognised mechanisms of action, further characteristics have been suggested, including an anti-inflammatory action via the impact on neuron–microglia axes responsible for inhibition of microglial activation. Therefore, in the present study, we sought to determine whether chronic treatment with chlorpromazine, quetiapine or aripiprazole could influence schizophrenia-like behavioural disturbances at the level of sensorimotor gating in male offspring prenatally exposed to LPS. Simultaneously, we wanted to explore if the chosen antipsychotics display a positive impact on the neuroimmunological parameters in the brains of these adult animals with a special focus on the ligand-receptor axes controlling neuron–microglia communication as well as pro- and anti-inflammatory factors related to the microglial activity. The results of our research revealed the beneficial effect of quetiapine on deficits in sensorimotor gating observed in prenatally LPS-exposed offspring. In terms of axes controlling neuron–microglia communication and markers of microglial reactivity, we observed a subtle impact of quetiapine on hippocampal Cx3cl1 and Cx3cr1 levels, as well as cortical Cd68 expression. Hence, further research is required to fully define and explain the involvement of quetiapine and other antipsychotics in Cx3cl1-Cx3cr1 and/or Cd200-Cd200r axes modulation and inflammatory processes in the LPS-based model of schizophrenia-like disturbances.

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Section: Discussionmentioning

confidence: 99%

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Chamera

Curzytek

Kamińska

et al. 2022

Cells

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“…The use of myeloid markers means that the findings were not able to definitively be accounted for by microglia only, implying the involvement of perivascular macrophages. Indeed, as mentioned by the authors in their study (Swanson et al, 2020), CD206 is specifically expressed by perivascular macrophages (De Picker et al, 2021;Shtaya et al, 2021).…”

Section: Microglial Studiesmentioning

confidence: 66%

Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

2022

Self Cite

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Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood–brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs, post-mortem studies, imaging and fluid biomarkers, genetics and transcriptomic data. In this review, we will discuss the advantages and limitations of these methods, highlighting the understanding these methods have brought the field on these cells communicative abilities, and the knowledge gaps that remain.

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“…В настоящее время одним из наиболее важных звеньев патогенеза шизофрении считается наличие хронического умеренного нейровоспаления, связанного с активацией микроглии параллельно с изменениями периферических иммунных маркеров [1,21,22]. Это представление основано на результатах исследования биомаркеров, таких как повышенный уровень провоспалительных цитокинов при первом эпизоде психоза и при хронической шизофрении [23,24].…”

Section: Introductionunclassified

Microglia-Oligodendrocyte Interactions in White Matter of the Prefrontal Cortex in Attack-Like Schizophrenia

Vikhreva

Rakhmanova

2023

Psychiatry

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Background: the authors previously reported the ultrastructural pathology of oligodendrocytes in contacts with microglia in white matter of the prefrontal cortex in attack-like schizophrenia supposedly associated with microglial activation. Aim of the study: to perform morphometry of the ultrastructural parameters of microglia in contact with oligodendrocytes and to analyze correlations between the parameters of microglia and oligodendrocytes previously studied in the schizophrenia group as compared to the control group. Material and methods: a postmortem ultrastructural morphometric study of microglia in contact with oligodendrocytes in white matter of the prefrontal cortex was performed in 8 cases of attack-like schizophrenia and 20 healthy controls. Group comparisons were performed using ANCOVA and Pearson correlation analyses. Results: we found reduced volume fraction (Vv) and the number of mitochondria and increased Vv, area and number of vacuoles of endoplasmic reticulum and area of heterochromatin in microglia in the schizophrenia group as compared to the control group. Area of microglial cytoplasm correlated positively with area and number of vacuoles in microglia, and Vv and the number of mitochondria in microglia correlated positively with Vv and the number of vacuoles in microglia in the schizophrenia but not in the control group. Positive correlations were found between area of lipofuscin granules in oligodendrocytes and areas of microglial cell, nucleus and cytoplasm and the number of mitochondria in microglia only in the schizophrenia group. Also, area of vacuoles in oligodendrocytes correlated positively with the number of mitochondria in microglia in the schizophrenia group. In contrast, in the control group but not in the schizophrenia group the parameters of mitochondria and lipofuscin granules correlated positively with the same parameters in oligodendrocytes. Conclusion: these data suggest that normal relationships between energy and lipid metabolism of microglia and oligodendrocytes are disturbed in schizophrenia. Dystrophic changes of oligodendrocytes in attack-like schizophrenia might be associated with the effects of microglial activation on lipid and protein metabolism.

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Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study

Cited by 30 publications

References 86 publications

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

Microglia-Oligodendrocyte Interactions in White Matter of the Prefrontal Cortex in Attack-Like Schizophrenia

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