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Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice
Sandra Giovanoli1, Harald Engler, Andrea Engler
1Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, 8603 Schwerzenbach, Switzerland.
Insights
Prenatal infection and peripuberty stress synergistically harm adult brain function and neurochemistry. Early life environmental insults interact, increasing vulnerability to neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Developmental Biology
Background:
- Prenatal infection and peripubertal trauma are linked to neuropsychiatric disorders.
- The cumulative effects of these environmental challenges on brain development and disease vulnerability are not well understood.
Purpose of the Study:
- To investigate the combined impact of prenatal immune challenge and peripubertal stress on brain function and behavior.
- To determine if early-life insults interact to increase susceptibility to neuropsychiatric conditions.
Main Methods:
- Utilized a translational mouse model to simulate prenatal infection and peripubertal stress.
- Assessed adult behavioral functions, neurochemistry, and brain immune responses.
Main Results:
- Combined prenatal and peripubertal exposures induced synergistic pathological effects on adult behavior and neurochemistry.
- Prenatal insult significantly heightened offspring vulnerability to stress-induced brain immune changes during peripuberty.
Conclusions:
- Adverse prenatal and peripubertal environmental factors interact, exacerbating risks for neuropsychiatric disorders.
- These findings support the 'multiple hits' hypothesis for delayed-onset mental illnesses.
Abstract:
Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.
