TY - JOUR
T1 - Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring
AU - Marwarha, Gurdeep
AU - Claycombe-Larson, Kate
AU - Schommer, Jared
AU - Ghribi, Othman
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health, Grant No. R01AG0145264, to Dr. Othman Ghribi. This work was also supported by USDA Agricultural Research Service, Project No. 3062-51000-052-00D, to Dr. Kate Claycombe.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Brain-derived neurotrophic factor
KW - Cyclic adenosine monophosphate
KW - Histone acetylation
KW - Histone methylation
KW - Maternal low-protein diet
KW - cAMP response element binding protein
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U2 - 10.1016/j.jnutbio.2017.03.005
DO - 10.1016/j.jnutbio.2017.03.005
M3 - Article
C2 - 28432877
AN - SCOPUS:85017631656
VL - 45
SP - 54
EP - 66
JO - Nutrition Reports International
JF - Nutrition Reports International
SN - 0955-2863
ER -