Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats.
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.
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.
Ting
T
Wu
Shining
S
Deng
Wei-Guang
WG
Li
Yongguo
Y
Yu
Fei
F
Li
Meng
M
Mao
D000818:Animals; D015153:Blotting, Western; D003072:Cognition Disorders / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D044343:Overnutrition / Q000150:complications; D010766:Phosphorylation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012193:Reversal Learning / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D050796:STAT3 Transcription Factor; D004298:Dopamine