Nature Reviews Neurology:
Maternal immune activation and abnormal brain development across CNS disorders (2014)
Maternal immune activation and abnormal brain development across CNS disorders (2014)
Maternal Immune Activation II
Maternal Immune Activation and "Long-Lasting Transcriptional Changes in Fetal Microglia"
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Abstract
In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. The cell types mediating the fetal brain response to maternal inflammation are largely unknown, hindering the development of novel treatment strategies. Here, we show that microglia, the resident phagocytes of the brain, highly express receptors for relevant pathogens and cytokines throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets. |
The many sources of maternal immune activation
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Val's Take/Conjecture
Autoimmune Disease is in a kind of weird relationship with Neuro-Developmental and Psychiatric Disorders.
Maternal immune activation and neuroinflammation in human neurodevelopmental disorders. (2021)
Maternal health during pregnancy plays a major role in shaping health and disease risks in the offspring. ...Diverse maternal inflammatory factors, including obesity, asthma, autoimmune disease, infection and psychosocial stress, are associated … 
See also: "Paternal Immune Activation":
Paternal immune activation by Poly I:C modulates sperm noncoding RNA profiles and causes transgenerational changes in offspring behavior. Brain Behav Immun. 2024 Paternal pre-conceptual environmental experiences, such as stress and diet, can affect offspring brain and behavioral phenotypes via epigenetic modifications in sperm. Furthermore, maternal immune activation due to infection during gestation can reprog … Maternal immune activation in neurodevelopmental disorders. (2018)
Developmental Dynamics "The mechanisms through which MIA increases the risk of neurodevelopmental disorders have become a subject of intensive research. "This review aims to describe how dysregulation of microglial function and immune mechanisms may link MIA and neurodevelopmental pathologi …" |
Researchers are on the verge of cracking the Neuro-Developmental/Psychiatric Continuum.
It is really about Maternal Immune Activation and the consequences of that over the life course. This is about the Brain and Central Nervous System, but it is really about the Immune System, as so many chronic illnesses are. Further, ADHD and Autism are DEVELOPMENTAL, but so are Schizophrenia and Bipolar Disorder. Some researchers also consider Depression a Neuro-Developmental Disorder. MIA and Kynurenine Metabolites and Pathway
Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder. T. Cells. 2023 Several studies show that genetic and environmental factors contribute to the onset and progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one of the major environmental factors driving this process. ...Activation o … |
Epigenetics, Maternal Immune Activation & Neuro-developmental Differences
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Val's Take/Conjecture
Recent advances in genetic and epigenetic research have underscored the significance of 5-hydroxymethylcytosine (5hmC) in neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and intellectual disability (ID), revealing its potential as both a biomarker for early detection and a target for novel therapeutic strategies.
This review article provides a comprehensive analysis of the role of 5hmC in NDDs by examining both animal models and human studies. By examining mouse models, studies have demonstrated that prenatal environmental challenges, such as maternal infection and food allergies, lead to significant epigenetic alterations in 5hmC levels, which were associated with
In human studies, researchers have linked alterations in 5hmC levels NDDs through studies in
specifically identifying significant epigenetic modifications in genes such as GAD1, RELN, FMR1 and EN-2, suggesting that dysregulation of 5hmC played a critical role in the pathogenesis of these disorders and highlighted the potential for targeted therapeutic interventions. Moreover, we explore the implications of these findings for the development of epigenetic therapies aimed at modulating 5hmC levels. The review concludes with a discussion on future directions for research in this field, such as machine learning, emphasizing the need for further studies to elucidate the complex mechanisms underlying NDDs and to translate these findings into clinical practice. This paper not only advances our understanding of the epigenetic landscape of NDDs but also opens up new avenues for diagnosis and treatment, offering hope for individuals affected by these conditions. |
Progress in Neurobiology
The link between maternal infection and these phenotypic changes is not fully understood, but there is increasing evidence that maternal immune activation induces prolonged immune alterations in the offspring’s brain which could underlie epigenetic alterations which in turn may mediate the behavior and brain changes. Maternal immune activation in rodent models: A systematic review of neurodevelopmental changes in gene expression and epigenetic modulation in the offspring brain. (2021)
Neurosci Biobehav Rev. Maternal immune activation (MIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. |