Lipopolysaccharide-induced maternal immune activation modulates microglial CX3CR1 protein expression and morphological phenotype in the hippocampus and dentate gyrus, resulting in cognitive inflexibility during late adolescence

Cossío, Lourdes Fernández de; Lacabanne, Chloé; Bordeleau, Maude; Castino, Garance; Kyriakakis, Phillip; Tremblay, Marie‐Ève

doi:10.1016/j.bbi.2021.07.025

Cited by 17 publications

(7 citation statements)

References 105 publications

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“…To our knowledge, it is the first time that transcriptional alterations of microglia-specific genes are reported in the associative striatum and hippocampus of individuals with SZ, although studies using animal models of SZ reported microglial alterations in these latter regions [ 42 – 45 ]. Remarkably, previous research suggested that striatal and hippocampal SZ-associated alterations involve dendritic spine loss, synaptic alterations and/or impaired neurogenesis [ 46 – 49 ], potentially through microglial dysfunction [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia

Fiorito,

Fakra,

Sescousse

et al. 2023

Transl Psychiatry

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Besides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related. Thus, we investigated the expression of a pre-registered list of 10 genes from a core signature of human microglia both at brain and peripheral levels. We included 9 independent Gene Expression Omnibus datasets (764 samples obtained from 266 individuals with schizophrenia and 237 healthy controls) from 8 different brain regions and 3 peripheral tissues. We report evidence of a widespread transcriptional alteration of microglia genes both in brain tissues (we observed a decreased expression in the cerebellum, associative striatum, hippocampus, and parietal cortex of individuals with schizophrenia compared with healthy controls) and whole blood (characterized by a mixed altered expression pattern). Our results suggest that brain underexpression of microglia genes may represent a candidate transcriptional signature for schizophrenia. Moreover, the dual brain-whole blood transcriptional alterations of microglia/macrophage genes identified support the model of schizophrenia as a whole-body disorder and lend weight to the use of blood samples as a potential source of biological peripheral biomarkers.

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Section: Discussionmentioning

confidence: 99%

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia

Fiorito,

Fakra,

Sescousse

et al. 2023

Transl Psychiatry

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“…LPS-exposed neonatal animals revealed detrimental effects in hippocampal neurogenesis from puberty to adulthood and showed the progression of ASD-like behaviors [ 162 ]. Alpha-glycosyl isoquercitrin (AGIQ) exerts chemo-preventive effects, such as antioxidant and anti-inflammatory effects.…”

Section: Hippocampal Neurogenesis-based Regenerative Therapy Proposed...mentioning

confidence: 99%

Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications

Liu

Gong

et al. 2023

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Autism spectrum disorder (ASD) is a cluster of heterogeneous neurodevelopmental condi- tions with atypical social communication and repetitive sensory-motor behaviors. The formation of new neurons from neural precursors in the hippocampus has been unequivocally demonstrated in the dentate gyrus of rodents and non-human primates. Accumulating evidence sheds light on how the deficits in the hippocampal neurogenesis may underlie some of the abnormal behavioral phenotypes in ASD. In this review, we describe the current evidence concerning pre-clinical and clinical studies supporting the significant role of hippocampal neurogenesis in ASD pathogenesis, discuss the possibility of improving hippocampal neurogenesis as a new strategy for treating ASD, and highlight the prospect of emerging pro‐neurogenic therapies for ASD.

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“…While this review focuses on studies performed in rodents, there is also a very strong nonhuman primate evidence in this field (refer to these reviews for more information [44][45][46]). Studies in rodents generally induce MIA with various inflammatory agents, including poly I:C, the bacterial endotoxin lipopolysaccharide (LPS), human influenza virus, and others [43,47,48]. Poly I:C is a synthetic double-stranded (ds) RNA analog of retroviral genomic dsRNA.…”

Section: Mia With Poly I:c: Insights From Rodent Modelsmentioning

confidence: 99%

The Outcomes of Maternal Immune Activation Induced with the Viral Mimetic Poly I:C on Microglia in Exposed Rodent Offspring

Loewen¹,

Chavesa²,

Murray³

et al. 2023

Dev Neurosci

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Maternal immune activation (MIA) can result from a variety of maternal inflammatory factors, including metabolic disorders, nutritional deficits, infections, and psychosocial stress. MIA has been consistently recognized as a major risk factor for neurodevelopmental disorders, and this association seems to be especially important for viral infections, as viral exposure during pregnancy was associated with a higher risk of developing neurodevelopmental disorders, such as schizophrenia. In MIA, the gestational parent’s inflammatory response to an immune stimulus alters or interrupts fetal development, triggering neurodevelopmental consequences. As MIA can occur in any pregnancy it is important to understand the many factors at play that contribute to altered brain development in the offspring, especially considering recent global events such as the COVID-19 pandemic. The underlying mechanisms by which MIA results in deleterious outcomes are not yet clear, but due to the inflammatory response it initiates, it is becoming apparent that microglia are critically involved. Through investigation of MIA animal models, the role of microglia in this field is becoming more evident. Compelling evidence from animal models indicates that MIA can disrupt synaptic pruning, neuronal progenitor cell proliferation /differentiation, oligodendrogenesis and more. Microglia appear as an active player, assisting these neural-related functions during healthy development, but also mediating MIA-induced disturbances in these critical processes when neurodevelopment is challenged. The present review illustrates this complex web by reviewing recent literature, focusing on the outcomes of MIA resulting from viral mimetic poly I:C in rodents, to provide a clear description of how MIA impacts microglial functions and what this means for the offspring’s neurodevelopment. Moreover, we discuss the possible implications of the COVID-19 pandemic on the neurodevelopment of the current and next generations in the frame of MIA models and propose some putative pharmacological and non-pharmacological approaches to prevent or attenuate MIA consequences.

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Lipopolysaccharide-induced maternal immune activation modulates microglial CX3CR1 protein expression and morphological phenotype in the hippocampus and dentate gyrus, resulting in cognitive inflexibility during late adolescence

Cited by 17 publications

References 105 publications

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia

Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications

The Outcomes of Maternal Immune Activation Induced with the Viral Mimetic Poly I:C on Microglia in Exposed Rodent Offspring

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