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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #341457

Research Project: Biology of Obesity Prevention

Location: Healthy Body Weight Research

Title: Maternal low protein decreases leptin expression in the brains of the neonatal rat offspring

Author
item Marwarha, Gurdeep - University Of North Dakota
item Larson, Kate
item Ghribi, Othman - University Of North Dakota

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/15/2017
Publication Date: 4/1/2017
Citation: Marwarha, G., Larson, K.J., Ghribi, O. 2017. Maternal low protein decreases leptin expression in the brains of the neonatal rat offspring [abstract]. Journal of Federation of American Societies for Experimental Biology. 31:lb474.

Interpretive Summary:

Technical Abstract: Prenatal exposure to a maternal low protein diet has been known to cause cognitive deficits in the adult progeny. Maternal low protein diets induce visual and spatial memmy impai1ment, deficits in learning and memo1y, as well as a host of behavioral abno1malities in the adult progeny. However, the underlying causes and the molecular mechanisms have not been identified. Herein, we demonstrate that a maternal low protein (LP) diet causes, in the brains of the male and female neonatal rat offspring, an attenuation in the basal expression of the Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuronal smvival and indispensable for learning and memory. Sprague-Dawley female rats were fed either a 20% no1mal protein diet (NP) or an 8% low protein (LP) diet inducted at three weeks before breeding and continued for the entirety of the gestation period. Maternal LP diet caused a significant reduction in the Bdnf expression in the whole brains of the male and female neonatal rat offspring. We delineated the molecular mechanisms fiuther, and found that a maternal LP diet - 1) decreases cAMP levels and the ensuing protein kinase A (PKA) activation, that 2) consequently reduces CREB activation, which 3) culminates in a significant reduction in cAMP response element binding protein (CREB) binding to the Bd,''f promoters - in the brains of male and female neonatal offspring. We finther show that prenatal exposure of the neonatal male and female offsp1ing to a maternal LP diet results iti a characteristic inactive or repressed exon I and exon IV promoter of the Bdnf gene in the brain, as evidenced by fluxes in signato1y hallmarks in the enrichment of acetylated and trimethylated histones in the nucleosomes that envelop the exon I and exon IV promoters of the Bdnf gene. Our study shows that prenatal exposure to a maternal LP diet results in the attenuation of basal Bdnf gene expression in the brains of the neonatal progeny through reduced activation of the cAMP/PKA/CREB pathway accompanied by changes in histone modification that make the exon I and exon IV promoter of the Bdnf gene refractory to transactivation.