MATERNAL immune activity during pregnancy influences offspring brain development, with sex-specific effects on memory circuitry lasting into midlife.
This study, conducted by researchers at Mass General Brigham and drawing from the New England Family Study (NEFS) cohort, examined the impact of prenatal immune environments on memory and brain health in offspring. Data from 204 participants, followed for over 50 years, revealed that elevated maternal levels of pro-inflammatory cytokines IL-6 and TNF-a during pregnancy were associated with adverse memory circuitry activity in offspring, particularly postmenopausal women, and linked to reduced cognitive performance in children as early as age seven. The study highlighted how sex differences in brain development shape the effects of prenatal exposures on long-term brain health.
Functional brain imaging was used to investigate the offspring’s memory regions, known to be dense with cytokine and sex hormone receptors. Findings showed that prenatal exposure to maternal pro-inflammatory cytokines significantly altered memory circuitry activity in a sex-specific manner. These effects persisted into midlife and correlated with increased inflammatory markers in postmenopausal women. Male offspring demonstrated distinct but less pronounced changes. Academic performance at age seven also correlated with later memory deficits, underscoring the lifelong implications of prenatal immune environments.
These findings suggest that maternal immune activity during pregnancy may predispose offspring to memory-related disorders, such as Alzheimer’s disease (AD), later in life. However, researchers emphasised that the brain’s adaptability offers a window for early intervention. Efforts are ongoing to identify biomarkers for early risk and resilience, aiming to inform targeted interventions during critical developmental periods such as puberty.
Future research will focus on clarifying mechanisms linking maternal immune activity to offspring brain development, exploring sex differences in aging and brain health, and examining how prenatal exposures interact with environmental factors. Understanding these pathways is vital for developing preventative strategies against memory disorders, particularly with a growing aging population.
Reference
Goldstein, JM et al. Prenatal immune origins of brain aging differ by sex. Mol Psychiatry. 2024;DOI:10.1038/s41380-024-02798-w.
