Sex-dependent behavioral deficits and neuropathology in a maternal immune activation model of autism

Obelia Haida1, Tareq Al Sagheer1, Anais Balbous1,2

  • 1Université de Poitiers, INSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, Poitiers, France.

Insights

Maternal immune activation in mice models autism spectrum disorder (ASD) and reveals males are more susceptible to social and motor deficits. Females show a protective effect against these developmental insults.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Immunology

Background:

  • Maternal immune activation (MIA) during pregnancy is linked to increased risk of neuropsychiatric disorders, including autism spectrum disorder (ASD).
  • ASD is a neurodevelopmental condition characterized by social communication deficits and restricted interests, affecting males more than females.
  • Motor disorders are frequently observed in ASD patients but are not primary diagnostic criteria.

Purpose of the Study:

  • To investigate the sex-specific effects of MIA on social and motor behaviors in a mouse model of ASD.
  • To examine the impact of MIA on brain regions controlling movement, including the nigro-striatal pathway, motor cortex, and cerebellum.

Main Methods:

  • Utilized the polyinosinic:polycytidylic acid (poly I:C) model to induce MIA in pregnant mice.
  • Assessed social interaction, motor development, and coordination in male and female offspring.
  • Quantified neuronal and cell populations in the motor cortex and cerebellum.

Main Results:

  • Male mice exposed to poly I:C exhibited more severe deficits in social interaction, motor development, and coordination compared to females.
  • Reduced Purkinje cell numbers in the cerebellum and motor cortex neurons were more pronounced in males.
  • Females demonstrated a greater resilience to the developmental effects of MIA.

Conclusions:

  • Sex differences exist in susceptibility to MIA-induced ASD-like behaviors and neuroanatomical changes.
  • Females appear to possess a protective mechanism against developmental insults leading to ASD.
  • The cerebellum and motor cortex are key brain regions affected by MIA, offering potential targets for managing ASD-related motor and social impairments.

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