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

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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2020-07, Vol.130 (7), p.3761-3776
Main Authors: Lippert, R N, Hess, S, Klemm, P, Burgeno, L M, Jahans-Price, T, Walton, M E, Kloppenburg, P, Brüning, J C
Format: Article
Language:English
Subjects:
Age
Animals
Attention deficit hyperactivity disorder
Biomedical research
Breastfeeding & lactation
Cognitive ability
Diet
Diet, High-Fat - adverse effects
Dopamine
Dopamine - metabolism
Dopamine D1 receptors
Dopamine D2 receptors
Female
Food intake
Gene expression
Genetic engineering
High fat diet
Hypothalamus
Lactation
Male
Males
Maternal Exposure - adverse effects
Mental disorders
Mesencephalon
Mesencephalon - metabolism
Mesencephalon - pathology
Metabolism
Mice
Mutation
Neostriatum
Neural networks
Neurons
Nutrition research
Obesity
Offspring
Phenotypes
Pregnancy
Scientific equipment industry
Sexual dimorphism
Spiny neurons
Sucrose
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI134412