Related Experiment Video
Updated: Jul 12, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Prenatal folate deficiency impairs sociability and memory/recognition in mice offspring
Misato Yoshikawa1, Katsuya Suemaru1
1School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.
Insights
Prenatal folate deficiency (FD) in mice impairs offspring sociability and memory. This is linked to reduced synaptic protein levels in the brain, suggesting a connection between maternal nutrition and neurodevelopmental outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Folate is crucial for fetal development and postnatal brain health.
- Folic acid supplementation is known to impact brain development and mental health.
- The link between maternal folate deficiency and child developmental disorders requires further investigation.
Purpose of the Study:
- To investigate the association between prenatal folate deficiency (FD) and neurodevelopmental disorders in offspring.
- To evaluate the impact of maternal folate intake on offspring behavior and synaptic protein expression.
Main Methods:
- ICR mice were fed either a control or folate-deficient diet from embryonic day 1 to parturition.
- Offspring behavior was assessed using tests for locomotor activity, anxiety, grooming, sociability, and learning/memory.
- Protein levels of NMDA receptors, AMPA receptors, PSD-95, and GAD65/67 were measured in the frontal cortex and hippocampus.
Main Results:
- Prenatal folate deficiency did not affect locomotor activity or anxiety levels.
- FD offspring exhibited impaired sociability, spatial memory, and novel object recognition.
- Reduced expression of AMPA receptor 1 and PSD-95 was observed in both the frontal cortex and hippocampus of FD mice.
- NMDA receptor subunit 2B and GAD65/67 were downregulated in the frontal cortex of FD mice.
Conclusions:
- Prenatal folate deficiency leads to behavioral deficits in offspring, including impaired social interaction and memory.
- FD is associated with reduced levels of key synaptic proteins in the frontal cortex and hippocampus.
- These findings highlight the critical role of maternal folate status in fetal neurodevelopment and suggest potential mechanisms for developmental disorders.
Abstract:
Folate is essential for the normal growth and development of the fetus. Folic acid supplementation during the fetal period affects postnatal brain development and reduces the incidence of mental disorders in animal and human studies. However, the association between folate deficiency (FD) during pregnancy and developmental disorders in children remains poorly understood. In this study, we investigated whether prenatal FD is associated with neurodevelopmental disorders in offspring. ICR mice were fed a control diet (2 mg folic acid/kg diet) or a folate-deficient diet (0.3 mg folic acid/kg diet) from embryonic day 1 until parturition. We evaluated locomotor activity, anxiety, grooming, sociability and learning memory in male offspring at 7-10 weeks of age. No differences were found in locomotor activity or anxiety in the open field test, nor in grooming time in the self-grooming test. However, sociability, spatial memory, and novel object recognition were impaired in the FD mice compared with control offspring. Furthermore, we measured protein expression levels of the NMDA and AMPA receptors, as well as PSD-95 and the GABA-synthesizing enzymes GAD65/67 in the frontal cortex and hippocampus. In FD mice, expression levels of AMPA receptor 1 and PSD-95 in both regions were reduced compared with control mice. Moreover, NMDA receptor subunit 2B and GAD65/67 were significantly downregulated in the frontal cortex of prenatal FD mice compared with the controls. Collectively, these findings suggest that prenatal FD causes behavioral deficits together with a reduction in synaptic protein levels in the frontal cortex and hippocampus.
