Related Experiment Video
Updated: Oct 22, 2025
Author Spotlight: Collecting the Brain and Serum from the Same Mice Fetus to Study Brain Tumor Development
Published on: May 17, 2024
Maternal High-Fat Diet Modulates Cnr1 Gene Expression in Male Rat Offspring
Dawid Gawliński1, Kinga Gawlińska1, Irena Smaga1
1Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
Insights
Maternal high-fat diet (HFD) exposure during pregnancy and lactation induced depressive-like behaviors in rat offspring. This diet altered CB1 receptor (Cnr1) gene expression and epigenetic modifications in key brain regions, impacting neurodevelopment.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- Maternal high-fat diet (HFD) is linked to neurodevelopmental and psychiatric disorders in offspring.
- Understanding the epigenetic mechanisms underlying these effects is crucial for early intervention.
Purpose of the Study:
- To investigate the impact of maternal HFD on depressive-like behavior in rat offspring.
- To analyze alterations in Cnr1 gene expression and associated epigenetic modifications (DNA methylation, microRNA levels) in specific brain regions.
Main Methods:
- Maternal HFD model in rats during gestation and lactation.
- Behavioral testing for depressive-like phenotype at postnatal days 28 and 63.
- Quantitative analysis of Cnr1 mRNA, miR-212-5p, miR-154-3p, and Cnr1 promoter methylation in prefrontal cortex, dorsal striatum, and hippocampus.
Main Results:
- Maternal HFD induced a depressive-like phenotype in offspring.
- Decreased Cnr1 expression in the prefrontal cortex and dorsal striatum, linked to increased miR-212-5p/miR-154-3p and promoter methylation.
- Conversely, increased Cnr1 expression in the hippocampus, associated with decreased miR-154-3p/miR-212-5p and promoter hypomethylation.
Conclusions:
- Maternal HFD triggers lasting epigenetic changes in offspring brain, influencing Cnr1 gene expression.
- These epigenetic alterations are associated with depressive-like behaviors, highlighting a potential mechanism for intergenerational effects.
- Dietary interventions during pregnancy may be critical for preventing HFD-induced neurodevelopmental consequences.
Abstract:
In recent years, strong evidence has emerged that exposure to a maternal high-fat diet (HFD) provokes changes in the structure, function, and development of the offspring's brain and may induce several neurodevelopmental and psychiatric illnesses. The aims of this study were to evaluate the effects of a maternal HFD during pregnancy and lactation on depressive-like behavior and Cnr1 gene expression (encoding the CB1 receptor) in brain structures of rat offspring and to investigate the epigenetic mechanism involved in this gene expression. We found that a maternal HFD during pregnancy and lactation induced a depressive-like phenotype at postnatal days (PNDs) 28 and 63. We found that a maternal HFD decreased the Cnr1 mRNA levels in the prefrontal cortex with the increased levels of miR-212-5p and methylation of CpG islands at the Cnr1 promoter and reduced the level of Cnr1 gene expression in the dorsal striatum with an increased level of miR-154-3p in adolescent male offspring. A contrasting effect of a maternal HFD was observed in the hippocampus, where upregulation of Cnr1 gene expression was accompanied by a decrease of miR-154-3p (at PNDs 28 and 63) and miR-212-5p (at PND 63) expression and methylation of CpG islands at the Cnr1 promoter in male offspring. In summary, we showed that a maternal HFD during pregnancy and lactation triggered several epigenetic mechanisms in the brains of rat offspring, which may be related to long-lasting alterations in the next generation and produce behavioral changes in offspring, including a depressive-like phenotype.
