Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice.

The Journal of Clinical Investigation
R N LippertJens C Brüning

Abstract

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.

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Citations

Jun 9, 2020·The Journal of Clinical Investigation·Yuki Yasumoto, Tamas L Horvath
Aug 6, 2020·International Journal of Molecular Sciences·Marie-Cécile Alexandre-GouabauVincent Paillé
Jan 21, 2021·Nutrients·Kyoko HasebeMargaret J Morris
Feb 18, 2021·Cell Reports·Montana H BooneMichael J Krashes
Jun 22, 2021·Trends in Endocrinology and Metabolism : TEM·Chloé BerlandGiuseppe Gangarossa
Jul 30, 2021·Neuroscience and Biobehavioral Reviews·Minerva Ortiz-ValladaresNorma Angélica Moy-López
Aug 5, 2020·Nature Neuroscience·Christopher M MazzoneMichael J Krashes

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Datasets Mentioned

BETA
GSE147469

Methods Mentioned

BETA
biopsies
Assay

Software Mentioned

Med Activity
ImageJ
GraphPad
Ensembl
GraphPad Prism
hisat
FIJI
cufflinks
NuAcc
cuffdiff

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