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Updated: Oct 1, 2025
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Prenatal allergic inflammation in rats programs the developmental trajectory of dendritic spine patterning in brain
Michaela R Breach1, Courtney N Dye1, Anabel Galan2
1Neuroscience Graduate Program, The Ohio State University, Columbus, OH, USA.
Insights
Prenatal allergic inflammation in mothers alters offspring brain development, affecting dendritic spine density in key regions. These changes may underlie neurodevelopmental disorders like ADHD and ASD, suggesting targets for future interventions.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal immune activation (MIA) during pregnancy is linked to increased risk of neurodevelopmental disorders (NDDs) in offspring, including Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD).
- Previous studies demonstrated that allergy-induced MIA in rats mimics NDD-associated behaviors and alters perinatal microglial development.
- Microglia are crucial for synaptic patterning, and altered synaptic architecture is observed in NDDs, highlighting the need to investigate MIA's impact on dendritic spines.
Purpose of the Study:
- To investigate the effects of allergic MIA on dendritic spine patterning dynamics across key forebrain regions involved in cognition and social behavior throughout neurodevelopment.
- To determine if MIA-induced alterations in dendritic spine density exhibit sex-specific patterns and developmental trajectories.
- To explore potential correlations between altered spine density and network disruptions in offspring exposed to prenatal allergic inflammation.
Main Methods:
- Adult female rats were sensitized to ovalbumin and challenged during pregnancy to induce allergic MIA.
- Offspring brains were collected at specific postnatal days (P5, P15, P30, P100-120) for Golgi-Cox staining.
- Dendritic spine density was quantified in the medial prefrontal cortex (mPFC), basal ganglia, septum, nucleus accumbens (NAc), and amygdala; correlational analyses were performed.
Main Results:
- Allergic MIA reduced dendritic spine density in the neonatal and juvenile mPFC, with normalization by P30. Sex-specific effects were observed in the septum and basal ganglia.
- MIA altered spine density in the nucleus accumbens across development, with reductions in juveniles and increases in adulthood, and decreased amygdala spine density in adults.
- Correlational analyses indicated MIA-induced disruptions in amygdala-related networks (neonatal) and cortico-striatal networks (juvenile/adult) in a sex-specific manner.
Conclusions:
- Prenatal allergic inflammation dynamically alters dendritic spine patterning in brain regions critical for cognition and social behavior throughout offspring development.
- These MIA-induced synaptic changes, exhibiting sex-specific patterns, may contribute to the pathophysiology of neurodevelopmental disorders.
- The findings provide a foundation for developing immunomodulatory interventions to target synaptic and behavioral deficits resulting from prenatal inflammatory exposures.
Abstract:
Allergic inflammation during pregnancy increases risk for a diagnosis of neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) in the offspring. Previously, we found a model of such inflammation, allergy-induced maternal immune activation (MIA), produced symptoms analogous to those associated with neurodevelopmental disorders in rats, including reduced juvenile play behavior, hyperactivity, and cognitive inflexibility. These behaviors were preceded by perinatal changes in microglia colonization and phenotype in multiple relevant brain regions. Given the role that microglia play in synaptic patterning as well as evidence for altered synaptic architecture in neurodevelopmental disorders, we investigated whether allergic MIA altered the dynamics of dendritic spine patterning throughout key regions of the rat forebrain across neurodevelopment. Adult virgin female rats were sensitized to the allergen, ovalbumin, with alum adjuvant, bred, and allergically challenged on gestational day 15. Brain tissue was collected from male and female offspring on postnatal days (P) 5, 15, 30, and 100-120 and processed for Golgi-Cox staining. Mean dendritic spine density was calculated for neurons in brain regions associated with cognition and social behavior, including the medial prefrontal cortex (mPFC), basal ganglia, septum, nucleus accumbens (NAc), and amygdala. Allergic MIA reduced dendritic spine density in the neonatal (P5) and juvenile (P15) mPFC, but these mPFC spine deficits were normalized by P30. Allergic inflammation reduced spine density in the septum of juvenile (P30) rats, with an interaction suggesting increased density in males and reduced density in females. MIA-induced reductions in spine density were also found in the female basal ganglia at P15, as well as in the NAc at P30. Conversely, MIA-induced increases were found in the NAc in adulthood. While amygdala dendritic spine density was generally unaffected throughout development, MIA reduced density in both medial and basolateral subregions in adult offspring. Correlational analyses revealed disruption to amygdala-related networks in the neonatal animals and cortico-striatal related networks in juvenile and adult animals in a sex-specific manner. Collectively, these data suggest that communication within and between these cognitive and social brain regions may be altered dynamically throughout development after prenatal exposure to allergic inflammation. They also provide a basis for future intervention studies targeted at rescuing spine and behavior changes via immunomodulatory treatments.
