Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats

Ting Wu; Shining Deng; Wei-Guang Li; Yongguo Yu; Fei Li; Meng Mao

doi:10.1371/journal.pone.0078876

Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats

PLoS One. 2013 Nov 4;8(11):e78876. doi: 10.1371/journal.pone.0078876. eCollection 2013.

Authors

Ting Wu¹, Shining Deng, Wei-Guang Li, Yongguo Yu, Fei Li, Meng Mao

Affiliation

¹ West China Second Hospital, Sichuan University, Chengdu, Sichuan, China ; Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China ; Chengdu Women's and Children's Central Hospital, Chengdu, Sichuan, China.

Abstract

Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Cognition Disorders / physiopathology
Corpus Striatum / metabolism
Corpus Striatum / physiopathology*
Dopamine / metabolism
Feeding Behavior / physiology
Female
Hypothalamus / metabolism
Male
Maternal Nutritional Physiological Phenomena
Motor Activity / physiology
Obesity / etiology
Obesity / physiopathology*
Overnutrition / complications
Phosphorylation
Pregnancy
Pregnancy Complications / physiopathology*
Prenatal Exposure Delayed Effects / physiopathology*
Rats
Rats, Wistar
Reversal Learning / physiology*
STAT3 Transcription Factor / metabolism

Substances

STAT3 Transcription Factor
Dopamine

Grants and funding

Ministry of Education of China (NCET program), National Science Foundation of China (81000592, 81222012, and 91232706), the National Basic Research Program of China (973 Project, 2013CB835100), Science and Technology Commission of Shanghai Municipality (10DZ2272200, 09DZ2200900, 10PJ1407500, 10PJ1403500, 10231203903 and 10JC1411200), Shanghai Municipal Education Commission (11ZZ103). Shanghai Municipal Health Bureau (2010004), Morning Star Rewarding Fund (Category B, 2011) of Shanghai Jiao Tong University and Xingbairen plan of Shanghai Jiao Tong University School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.