Maternal Immune Activation by Poly I:C as a preclinical Model for Neurodevelopmental Disorders: A focus on Autism and Schizophrenia

Haddad, Faraj L.; Patel, Salonee V.; Schmid, Susanne

doi:10.1016/j.neubiorev.2020.04.012

Cited by 139 publications

(133 citation statements)

References 319 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…MIA alters the development of the dopaminergic system and many other neurotransmitter systems and brain regions (5,6,79,80). Maternal cytokines, particularly IL-6, are central in mediating these effects (5).…”

Section: Discussionmentioning

confidence: 99%

“…Maternal infections and other environmental risk factors for SCZ and neurodevelopmental disorders may independently account for a few clinical cases since exposure to them does not always generate the disorder or are implicated in several psychiatric illnesses ( 6 , 39 , 79 , 80 , 176 , 177 ). In this regard, heterogeneity of response characterizes all known environmental risk factors for psychopathology, including the most overwhelming of traumas ( 176 ).…”

Section: Discussionmentioning

confidence: 99%

“…An overall trend regarding these two phenotypes is one where PPI deficits are more consistently observed when MIA occurs at gestational stages earlier than GD 16 in both mice and rats. At the same time, hyper-responsiveness to activators of the mesolimbic dopaminergic system appears when challenging the mothers at any developmental age [reviewed in (79)].…”

Section: Viral Mimetic Poly I:cmentioning

confidence: 99%

“…The viral mimic polyinosinic:polycytidylic acid (poly I:C) has been used to stimulate the maternal immune system (with one or multiple injections), at several stages of pregnancy in mice or rats, ranging from GD 8.5 until GD 18.5. The effects of these prenatal treatments have been extensively reviewed elsewhere ( 6 , 7 , 79 – 81 ); thus, we will focus on those consequences more closely relevant for psychosis. Prenatal stimulation with poly I:C induced deficits in an operational measure of sensorimotor gating ( 82 ), pre-pulse inhibition of acoustic startle and increased sensitivity to the locomotor activating effects of cocaine, AMPH and methamphetamine, whose locomotor effects depend on the mesolimbic DA system ( 83 – 105 ).…”

Section: Animal Models Of Maternal Infectionmentioning

confidence: 99%

See 3 more Smart Citations

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

2020

View full text Add to dashboard Cite

Prenatal infections have been linked to the development of schizophrenia (SCZ) and other neurodevelopmental disorders in the offspring, and work in animal models indicates that this is to occur through the maternal inflammatory response triggered by infection. Several studies in animal models demonstrated that acute inflammatory episodes are sufficient to trigger brain alterations in the adult offspring, especially in the mesolimbic dopamine (DA) system, involved in the pathophysiology of SCZ and other disorders involving psychosis. In the current review, we synthesize the literature on the clinical studies implicating prenatal infectious events in the development of SCZ. Then, we summarize evidence from animal models of maternal immune activation (MIA) and the behavioral and molecular alterations relevant for the function of the DAergic system. Furthermore, we discuss the evidence supporting the involvement of maternal cytokines, such as interleukin 6 (IL-6) and leptin (a hormone with effects on inflammation) in mediating the effects of MIA on the fetal brain, leading to the long-lasting effects on the offspring. In particular, IL-6 has been involved in mediating the effects of MIA animal models in the offspring through actions on the placenta, induction of IL-17a, or triggering the decrease in non-heme iron (hypoferremia). Maternal infection is very likely interacting with additional genetic and environmental risk factors in the development of SCZ; systematically investigating how these interactions produce specific phenotypes is the next step in understanding the etiology of complex psychiatric disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Viral Mimetic Poly I:cmentioning

confidence: 99%

Section: Animal Models Of Maternal Infectionmentioning

confidence: 99%

See 2 more Smart Citations

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

2020

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated the impact of various maternal exposures, including maternal stress, metabolic disorders, air pollution, and infections, on fetal brain development. [2][3][4]7 Such exposures may lead to offspring neurodevelopmental morbidity via maternal immune activation, [36][37][38][39][40][41][42][43] which results in aberrant microglial programming in the developing brain. [12][13][14][15]18 In turn, maternal immune activation models have pointed to aberrant differentiation of fetal microglia and dysregulation of cytokine networks as key mechanisms underlying abnormal fetal brain development, with microglia primed toward a pro-inflammatory phenotype and altered synaptic pruning implicated in offspring morbidity.…”

Section: Cb-imgs Derived From Cb-mncs Exposed To Maternal Sars-cov-2 mentioning

confidence: 99%

Umbilical cord blood derived microglia-like cells to model COVID-19 exposure

Sheridan

Thanos

Guzman

et al. 2020

Preprint

View full text Add to dashboard Cite

Microglia, the resident brain immune cells, play a critical role in normal brain development, and are impacted by the intrauterine environment, including maternal immune activation and inflammatory exposures. The COVID-19 pandemic presents a potential developmental immune challenge to the fetal brain, in the setting of maternal SARS-CoV-2 infection with its attendant potential for cytokine production and, in severe cases, cytokine storming. There is currently no biomarker or model for in utero microglial priming and function that might aid in identifying the neonates and children most vulnerable to neurodevelopmental morbidity, as microglia remain inaccessible in fetal life and after birth. This study aimed to generate patient-derived microglial-like cell models unique to each neonate from reprogrammed umbilical cord blood mononuclear cells, adapting and extending a novel methodology previously validated for adult peripheral blood mononuclear cells. We demonstrate that umbilical cord blood mononuclear cells can be used to create microglial-like cell models morphologically and functionally similar to microglia observed in vivo. We illustrate the application of this approach by generating microglia from cells exposed and unexposed to maternal SARS-CoV-2 infection. Our ability to create personalized neonatal models of fetal brain immune programming enables non-invasive insights into fetal brain development and potential childhood neurodevelopmental vulnerabilities for a range of maternal exposures, including COVID-19.

show abstract

Age‐related changes in behavior profile in male offspring of rats treated with poly I:C‐induced maternal immune activation in early gestation

Chen,

Meng,

Fang

et al. 2024

Anim Models and Exp Med

View full text Add to dashboard Cite

BackgroundAutism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy. It is still unclear whether behavior phenotypes change at different developmental stages in offspring following the activation of the maternal immune system.MethodsSprague–Dawley rats received a single caudal vein injection of 10 mg/kg polyinosinic:polycytidylic acid (poly I:C) on gestational day 9 and the offspring were comprehensively tested for behaviors in adolescence and adulthood.ResultsMaternal serum levels of interleukin (IL)‐6, IL‐1β and tumor necrosis factor‐α were elevated in poly I:C‐treated dams. The offspring of maternal poly I:C‐induced rats showed increased anxiety, impaired social approach, and progressive impaired cognitive and sensorimotor gating function.ConclusionMaternal immune activation led to developmental specificity behavioral impairment in offspring.

show abstract

Maternal Immune Activation by Poly I:C as a preclinical Model for Neurodevelopmental Disorders: A focus on Autism and Schizophrenia

Cited by 139 publications

References 319 publications

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

Umbilical cord blood derived microglia-like cells to model COVID-19 exposure

Age‐related changes in behavior profile in male offspring of rats treated with poly I:C‐induced maternal immune activation in early gestation

Contact Info

Product

Resources

About