Universität zu Köln

Lippert, R. N., Hess, S., Klemm, P., Burgeno, L. M., Jahans-Price, T., Walton, M. E., Kloppenburg, P. and Bruening, J. C. (2020). Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice. J. Clin. Invest., 130 (7). S. 3761 - 3777. ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 1558-8238

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lippert, R. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klemm, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burgeno, L. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jahans-Price, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Walton, M. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, J. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-327185
DOI:	10.1172/JCI134412
Journal or Publication Title:	J. Clin. Invest.
Volume:	130
Number:	7
Page Range:	S. 3761 - 3777
Date:	2020
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	1558-8238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GESTATIONAL WEIGHT-GAIN; PARKINSONS-DISEASE; BRAIN-DEVELOPMENT; SUBSTANTIA-NIGRA; GENE-EXPRESSION; NERVOUS-SYSTEM; OBESITY; NEURONS; RECEPTOR; LEPTIN Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32718