Maternal Immune Activation

Dec. 2020

Japan's Kobe University School of Medicine makes more progress in understanding ----

​Maternal Immune Activation as a source of cognitive Disability

Maternal immune activation induces sustained changes in fetal microglia motility

Abstract

Maternal infection or inflammation causes abnormalities in brain development associated with subsequent cognitive impairment and in an increased susceptibility to schizophrenia and autism spectrum disorders.

Maternal immune activation (MIA) and increases in serum cytokine levels mediates this association via effects on the fetal brain, and microglia can respond to maternal immune status, but consensus on how microglia may respond is lacking and no-one has yet examined if microglial process motility is impaired.

In this study we investigated how MIA induced at two different gestational ages affected microglial properties at different developmental stages.

Immune activation in mid-pregnancy increased IL-6 expression in embryonic microglia, but failed to cause any marked changes in morphology either at E18 or postnatally.

In contrast MIA, particularly when induced earlier (at E12), caused sustained alterations in the patterns of microglial process motility and behavioral deficits.

Our research has identified an important microglial property that is altered by MIA and which may contribute to the underlying pathophysiological mechanisms linking maternal immune status to subsequent risks for cognitive disease.
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Kobe University Health Sciences Center in Japan

Maternal Immune activation ---

alteration of the gut microbiome & psychiatric Disorders

Abstract

Maternal immune activation (MIA) has been identified as a causal factor in psychiatric disorders by epidemiological studies in humans and mechanistic studies in rodent models.

Addressing this gap in species between mice and human will accelerate the understanding of the role of MIA in the etiology of psychiatric disorders.

Here, we provide the first study of MIA in the ferret (Mustela putorius furo), an animal model with a rich history of developmental investigations due to the similarities in developmental programs and cortical organization with primates.

We found that after MIA by injection of PolyIC in the pregnant mother animal, the adult offspring exhibited reduced social behavior, less eye contact with humans, decreased recognition memory, a sex-specific increase in amphetamine-induced hyperlocomotion, and altered gut microbiome.

We also studied the neurophysiological properties of the MIA ferrets in development by in-vivo recordings of the local field potential (LFP) from visual cortex in five- to six-week-old animals, and found that the spontaneous and sensory-evoked LFP had decreased power, especially in the gamma frequency band.

Overall, our results provide the first evidence for the detrimental effect of MIA in ferrets and support the use of the ferret as an intermediate model species for the study of disorders with neurodevelopmental origin.

​Affiliations
  • 1Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 2Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 3Neuroscience Center Bioinformatics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 4Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 5Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 6Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
  • 7Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

Strain differences in the susceptibility to the gut-brain axis and neurobehavioural alterations induced by maternal immune activation in mice (2018)

Abstract

There is a growing realization that the severity of the core symptoms of autism spectrum disorders and schizophrenia is associated with gastrointestinal dysfunction.

Nonetheless, the mechanisms underlying such comorbidities remain unknown.

Several genetic and environmental factors have been linked to a higher susceptibility to neurodevelopmental abnormalities.

The maternal immune activation (MIA) rodent model is a valuable tool for elucidating the basis of this interaction.

We induced MIA with polyinosinic-polycytidylic acid (poly I:C) at gestational day 12.5 and assessed behavioural, physiological and molecular aspects relevant to the gut-brain axis in the offspring of an outbred (NIH Swiss) and an inbred (C57BL6/J) mouse strain.

Our results showed that the specific MIA protocol employed induces social deficits in both strains.

However, alterations in anxiety and depression-like behaviours were more pronounced in NIH Swiss mice.

These strain-specific behavioural effects in the NIH Swiss mice were associated with marked changes in important components of gut-brain axis communication: the endocrine response to stress and gut permeability.

In addition, MIA-induced changes in vasopressin receptor 1a mRNA expression in the hypothalamus were observed in NIH Swiss mice only. Taken together, these data suggest that genetic background is a critical factor in susceptibility to the gut-brain axis effects induced by MIA.

​Affiliations
  • 1APC Microbiome Institute.
  • 2Departments of Anatomy and Neuroscience.
  • 3Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.

Autoimmunity, Epigenetics, Genetics & Infections

Pain Relievers, Alcohol and Smoking

Epidurals and caesarian sections

Developmental Disabilities & Mental Illness