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Many neurodevelopmental disorders have a higher
incidence in men, whereas autoimmune diseases are
more prevalent in women: while the underlying
mechanisms and consequences remain to be discovered,
a new Inserm study reveals a key role of microglia
at the brain/environment interface and shows that
males and females have distinct susceptibilities
time windows to microbiome alterations.
The microglia, which are known players in brain
development and functioning, differentially respond
to microbiome perturbations in male or female mice.
Microglia are immune cells that respond to traumatic
injury or inflammatory signals to protect the brain,
acting as sensors of various environmental signals.
In addition to their role as immune sentinels,
microglia have also been show to regulate several
steps of brain wiring and functioning.
Consistently, microglia dysfunction has been linked
with the etiology of several neurodegenerative
diseases and neurodevelopmental disorders, including
Schizophrenia or Autism Spectrum Disorders.
Microglia therefore play major roles in brain
circuits and could constitute an entry point for
environmental signals.
To test this hypothesis, Morgane Thion and Sonia
Garel, Inserm researchers from IBENS (Institute of
Biology of the Ecole Normale Supérieure – Inserm/CNRS/ENS)
in Paris and researchers from SIgN (Singapore
Immunology Network, A*STAR) in Singapore, used a
multidisciplinary approach involving germ-free mice,
which lack all the microbiome, and adult mice
treated with antibiotics, which acutely destroys the
gut flora.
Through a combination of global genomic analyses and
histological studies, researchers have shown that
microglia are profoundly affected by microbiota
disruption, already from prenatal stages.
Strikingly, the impact of the microbiome on
microglia depended on the sexual identity and the
age: microglia of males were perturbed prenatally
whereas those of females were affected in adulthood.
This surprising sexual dimorphism echoes the fact
that many neurodevelopmental disorders have a higher
incidence in men, whereas autoimmune diseases are
more prevalent in women.
While the underlying mechanisms and consequences
remain to be discovered, this study reveals a key
role of microglia at the brain/environment interface
and shows that males and females have distinct
susceptibilities time windows to microbiome
alterations.
For the authors, these elements should be
systematically taken into consideration at
preclinical and clinical level.
For more information
Cell
Microbiome Influences Prenatal and Adult Microglia
in a Sex-Specific Manner
Link...
Inserm -Institut national de la santé et de la
recherche médicale
Link...
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