Inflammation stresses out brain development

Zengeler, Kristine E.; Lukens, John R.

doi:10.1038/s41593-020-00775-4

Cited by 4 publications

(5 citation statements)

References 14 publications

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“…The HPA axis responds to a wide variety of maternal signals that disrupt fetomaternal equilibrium. In particular, maternal immune activation (MIA) during pregnancy by pathogen-derived stimuli, autoinflammatory conditions or environmental irritants ( 85 ) might be an important contributor to fetal or early life neurodevelopmental disorders such as spectrum autism disorders and schizophrenia ( 86 – 88 ). For a latest review see Depino A., 2018 ( 89 ).…”

Section: Inflammation and Activation Of The Hpa Axismentioning

confidence: 99%

“…As inflammatory mediators can pass through fetal blood-brain barrier they can cause neuroinflammation leading to neuronal loss, white matter abnormalities and impaired synaptic development and neurotransmission ( 92 ). In addition, studies in rodents suggest that MIA during pregnancy can also result in profound changes in protein synthesis of the fetal brain (involving translation initiation factors and other regulators of protein synthesis) disrupting the neurodevelopment of the fetus ( 85 ). MIA due to environmental insults by endocrine disrupting chemicals (EDCS) can also affect the developing embryo by altering synaptic connectivity, neurotransmitter or neuropeptide expression, and neuronal differentiation ( 93 ).…”

Section: Inflammation and Activation Of The Hpa Axismentioning

confidence: 99%

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Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

et al. 2021

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Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s hypothalamic–pituitary–adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.

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Section: Inflammation and Activation Of The Hpa Axismentioning

confidence: 99%

Section: Inflammation and Activation Of The Hpa Axismentioning

confidence: 99%

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

et al. 2021

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“…A recent study harnessed single-cell RNA sequencing technology to better understand the molecular mechanisms underlying MIA following Poly I:C exposure and again, found sexually dimorphic effects between male and female offspring (Kalish et al, 2021). Kalish et al (2021) observed marked sex-specificity in the context of proteostasis and the integrated stress response (ISR) -another relevant mechanism recently implicated in the etiology of NDDs gaining momentum (Lombardo et al, 2018;Advani and Ivanov, 2019;Chen et al, 2019;Zengeler and Lukens, 2021). In brief, Kalish et al (2021) observed the activation of the ISR triggered by ER stress, to be at the core of social and repetitive behavioral deficits in male MIA offspring.…”

Section: Male Vulnerability and Female Resiliencementioning

confidence: 99%

A comprehensive approach to modeling maternal immune activation in rodents

et al. 2022

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Prenatal brain development is a highly orchestrated process, making it a very vulnerable window to perturbations. Maternal stress and subsequent inflammation during pregnancy leads to a state referred to as, maternal immune activation (MIA). If persistent, MIA can pose as a significant risk factor for the manifestation of neurodevelopmental disorders (NDDs) such as autism spectrum disorder and schizophrenia. To further elucidate this association between MIA and NDD risk, rodent models have been used extensively across laboratories for many years. However, there are few uniform approaches for rodent MIA models which make not only comparisons between studies difficult, but some established approaches come with limitations that can affect experimental outcomes. Here, we provide researchers with a comprehensive review of common experimental variables and potential limitations that should be considered when designing an MIA study based in a rodent model. Experimental variables discussed include: innate immune stimulation using poly I:C and LPS, environmental gestational stress paradigms, rodent diet composition and sterilization, rodent strain, neonatal handling, and the inclusion of sex-specific MIA offspring analyses. We discuss how some aspects of these variables have potential to make a profound impact on MIA data interpretation and reproducibility.

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“…Since the discovery that ASD might have an inflammatory etiology, among the others, some researchers of the immunology field have focused on finding the immunological aspects of ASDs pathogenesis. 40 The majority of studies conducted so far have been considering inflammatory cytokines and there are a few studies that have addressed the immuno-metabolic interactions in ASD pathogenesis. 41 , 42 …”

Section: Introductionmentioning

confidence: 99%

“…39 Since the discovery that ASD might have an inflammatory etiology, among the others, some researchers of the immunology field have focused on finding the immunological aspects of ASDs pathogenesis. 40 The majority of studies conducted so far have been considering inflammatory cytokines and there are a few studies that have addressed the immuno-metabolic interactions in ASD pathogenesis. 41,42 Among the inflammatory mediators are the adipokines which are chemicals mainly secreted by the adipose tissue as well as some immune cells and subsequently impact immune responses in health and diseases such as ASD.…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF-related protein-1: Potential biomarker for early diagnosis of autism spectrum disorder

Raeisy

Bayati

Noorbakhsh

et al. 2022

Int J Immunopathol Pharmacol

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Introduction Autism spectrum disorders (ASDs) are neurodevelopmental diseases characterized by communication inabilities, social interaction impairment, repetitive behavior, as well as learning problems. Although the exact mechanism underlying this disease is still obscure, researchers believe that several factors play a significant role in its development and pathogenesis. Some authors have reported an association between adipokines family and autism. C1q/TNF-related protein-1 (CTRP1) is a member of the adipokines family, and we hypothesized that this adipokine might have an influential role in the pathogenesis of ASDs. Since there is no specific marker for screening the disease, we evaluated CTRP1 as a potential marker for achieving this purpose. Methods Blood samples were collected from 82 (41 ASDs boys, 41 healthy boys as controls) children aged 5–7 years old. CTRP1 gene expression and CTRP1 serum level were measured by quantitative realtime-PCR and enzyme-linked immunosorbent assay methods, respectively. Results It was found that CTRP1 is significantly elevated in autistic children in comparison to healthy controls, both at the gene expression level, as well as at the serum level; demonstrating a good diagnostic value with a good range of sensitivity and specificity for detecting ASDs. Conclusion CTRP1 expression is elevated in ASDs boys aged 5–7 years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.

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Inflammation stresses out brain development

Cited by 4 publications

References 14 publications

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment

A comprehensive approach to modeling maternal immune activation in rodents

C1q/TNF-related protein-1: Potential biomarker for early diagnosis of autism spectrum disorder

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