U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

PubAg

Main content area

Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring

Author:
Gurdeep Marwarha, Kate Claycombe-Larson, Jared Schommer, Othman Ghribi
Source:
Journal of nutritional biochemistry 2017 v.45 pp. 54-66
ISSN:
0955-2863
Subject:
memory, nucleosomes, transcriptional activation, histones, cyclic AMP, brain, breeding, signal transduction, binding proteins, gestation period, cAMP-dependent protein kinase, low protein diet, maternal exposure, memory disorders, progeny, neonates, exons, females, rats
Abstract:
Prenatal exposure to a maternal low-protein (LP) diet has been known to cause cognitive impairment, learning and memory deficits. However, the underlying mechanisms have not been identified. Herein, we demonstrate that a maternal LP diet causes, in the brains of the neonatal rat offspring, an attenuation in the basal expression of the brain-derived neurotrophic factor (BDNF), a neurotrophin indispensable for learning and memory. Female rats were fed either a 20% normal protein (NP) diet or an 8% LP 3 weeks before breeding and during the gestation period. Maternal LP diet caused a significant reduction in the Bdnf expression in the brains of the neonatal rats. We further found that the maternal LP diet reduced the activation of the cAMP/protein kinase A/cAMP response element binding protein (CREB) signaling pathway. This reduction was associated with a significant decrease in CREB binding to the Bdnf promoters. We also show that prenatal exposure to the maternal LP diet results in an inactive or repressed exon I and exon IV promoter of the Bdnf gene in the brain, as evidenced by fluxes in signatory hallmarks in the enrichment of acetylated and trimethylated histones in the nucleosomes that envelop the exon I and exon IV promoters, causing the Bdnf gene to be refractory to transactivation. Our study is the first to determine the impact of a maternal LP diet on the basal expression of BDNF in the brains of the neonatal rats exposed prenatally to an LP diet.
Agid:
5667790
Handle:
10113/5667790