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Maternal Metabolic Programming of the Developing Central Nervous System: Unified Pathways to Metabolic and
Rachel N Lippert1, Jens C Brüning2
1German Institute of Human Nutrition Potsdam Rehbrücke, Potsdam, Germany; German Center for Diabetes Research, Neuherberg, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany.
Insights
Maternal obesity and type 2 diabetes during pregnancy can negatively impact offspring brain development, potentially leading to metabolic and psychiatric disorders. Understanding these developmental effects is crucial for early intervention.
Area of Science:
- Neuroscience
- Developmental Biology
- Metabolic Disorders
Background:
- The perinatal period is a sensitive window where maternal health significantly influences offspring development.
- Maternal obesity and type 2 diabetes mellitus (T2DM) are increasingly recognized as critical environmental factors affecting fetal brain development.
- While adult brain effects of obesity are known, developmental impacts from maternal overnutrition are less understood.
Purpose of the Study:
- To review current advancements in understanding how maternal metabolic state programs offspring brain development.
- To highlight the impact of maternal obesity and T2DM on fetal brain structure, function, and connectivity.
- To identify critical developmental windows and peripheral factors involved in these programming effects.
Main Methods:
- This review synthesizes findings from preclinical and clinical studies examining maternal metabolic conditions and offspring neurodevelopment.
- Focuses on research investigating brain connectivity, regional development, and molecular changes in the fetal brain.
- Includes analysis of peripheral contributors and potential intervention strategies.
Main Results:
- Maternal overnutrition and metabolic dysfunction can lead to sustained alterations in offspring brain development, affecting neural connectivity and specific brain regions.
- These changes are linked to an increased predisposition to metabolic and psychiatric diseases in offspring.
- Emerging evidence points to peripheral factors and specific developmental time windows as key mediators.
Conclusions:
- Maternal metabolic health during gestation critically influences fetal brain development and long-term health outcomes.
- Understanding the cellular and molecular mechanisms is vital for developing targeted interventions to mitigate risks associated with maternal obesity and T2DM.
- Further research into peripheral contributors and critical intervention windows is warranted to prevent neurodevelopmental and metabolic diseases.
Abstract:
The perinatal period presents a critical time in offspring development where environmental insults can have damaging impacts on the future health of the offspring. This can lead to sustained alterations in offspring development, metabolism, and predisposition to both metabolic and psychiatric diseases. The central nervous system is one of the most sensitive targets in response to maternal obesity and/or type 2 diabetes mellitus. While many of the effects of obesity on brain function in adults are known, we are only now beginning to understand the multitude of changes that occur in the brain during development on exposure to maternal overnutrition. Specifically, given recent links between maternal metabolic state and onset of neurodevelopmental diseases, the specific changes that are occurring in the offspring are even more relevant for the study of disease onset. It is therefore critical to understand the developmental effects of maternal obesity and/or type 2 diabetes mellitus and further to define the underlying cellular and molecular changes in the fetal brain. This review focuses on the current advancements in the study of maternal programming of brain development with particular emphasis on brain connectivity, specific regional effects, newly studied peripheral contributors, and key windows of interventions where maternal bodyweight and food intake may drive the most detrimental effects on the brain and associated metabolic and behavioral consequences.
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