Location: Healthy Body Weight ResearchTitle: Prenatal exposure to a maternal LP diet decreases BDNF expression in the brains of the neonatal offspring
|MARWARHA, GURDEEP - University Of North Dakota|
|LILEK, JACLYN - University Of North Dakota|
|GHRIBI, OTHMAN - University Of North Dakota|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2016
Publication Date: 4/1/2017
Citation: Marwarha, G., Larson, K.J., Lilek, J., Ghribi, O. 2017. Prenatal exposure to a maternal LP diet decreases BDNF expression in the brains of the neonatal offspring [abstract]. Journal of Federation of American Societies for Experimental Biology. 31:644.13.
Technical Abstract: Maternal low protein (LP) diets during gestation cause learning and mernmy impai1ment as well as cognitive deficits in the neonatal and adult offsp1ing. The cellular and molecular mechanism that mediate the deleterious effects of prenatal exposure to a maternal LP diet on cognitive function is egregiously understood. Leptin, an adipocytokine expressed endogenously in the brain, exhibits pleiotropic effects in the brain and plays an indispensable role in learning and memo1y, as well as neuronal smvival. In this study, we show that prenatal exposure to a maternal LP diet results in the mitigation of basal expression of leptin in the brains of the neonatal rat offsp1ing. Sprague-Dawley female rats were fed either a 20% normal protein diet (NP) or an 8% low protein (LP) diet inducted at three weeks before breeding and continued for the entirety of the gestation pe1iod. Prenatal exposure to a maternal LP diet resulted in reduced leptin expression in the brains of the neonatal offspring that was ascribed to a reduction in the C/EBPa and C/EBPP - mediated transactivation of the leptin promoter. We fu1ther delved into and delineated the upstream molecular mediators and elucidated the role of lower CREB-mediated transc1iption of C/EBPa and C/EBPP that resulted in a reduction of the basal expression of C/EBPa and C/EBPP leading to a significant attenuation in their transctiptional activities in the brains of the neonatal progeny prenatally exposed to a maternal LP diet. This decrease in transcriptional activity of C/EBPa and C/EBPP results in the attenuation of the basal leptin promoter activity. Fmthe1more, matemal LP diet also induces a reduction in the enrichment of the acetylated histones in the nucleosomes that envelope the leptin promoter thereby making it refractory to trans-activation. Our study unveils a mitigation of leptin expression in the brain as a novel mechanistic insight and a conduit into the deleterious effects evoked by prenatal exposure to a maternal LP diet on cognitive function.