Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Hypertensive disorders of pregnancy (HDP) increase offspring risk for neurodevelopmental and neurobehavioral disorders.
• Rodent models of Preeclampsia (PreE) and HELLP syndrome were used to study adolescent offspring behavior.
• T-cell activation inhibitors, like Orencia, were investigated for their potential to mitigate HDP-induced effects.

Purpose of the Study:

• To investigate the behavioral outcomes in adolescent offspring of rodent models of PreE and HELLP.
• To determine if maternal treatment with Orencia impacts offspring neurobehavioral development.
• To explore sex-dependent differences in offspring neurodevelopment following HDP and maternal immune modulation.

Main Methods:

• Utilized rodent models of Preeclampsia and HELLP syndrome.
• Administered Orencia, a T-cell activation inhibitor, to a subset of pregnant dams.
• Assessed offspring behavior using social, cognitive (Barnes Maze), and locomotor tests.
• Analyzed adult brain tissue for myelin basic protein (MBP) and NeuN expression.

Main Results:

• Offspring from hypertensive dams exhibited cognitive deficits on the Barnes Maze test.
• Maternal Orencia treatment showed sex-dependent effects on play behavior.
• No significant differences in MBP or NeuN expression were observed in the prefrontal cortex or hippocampus across groups.

Conclusions:

• Hypertensive disorders of pregnancy are associated with significant behavioral changes, especially cognitive differences, in offspring.
• Neurobehavioral development in offspring is influenced by the type of HDP and maternal immune system alterations.
• Sex-dependent differences in offspring neurobehavioral outcomes were observed, suggesting complex interactions.