摘要：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.
