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

Gurdeep Marwarha, Kate Claycombe-Larson, Jared Schommer, Ghribi Othman

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)54-66
Number of pages13
JournalJournal of Nutritional Biochemistry
Volume45
DOIs
StatePublished - Jul 1 2017

Fingerprint

Protein-Restricted Diet
Brain-Derived Neurotrophic Factor
Nutrition
Rats
Brain
Mothers
Exons
Proteins
Cyclic AMP Response Element-Binding Protein
Learning
Maternal Exposure
Genes
Nucleosomes
Memory Disorders
Nerve Growth Factors
Cyclic AMP-Dependent Protein Kinases
Data storage equipment
Protein Binding
Histones
Transcriptional Activation

Keywords

  • Brain-derived neurotrophic factor
  • Cyclic adenosine monophosphate
  • Histone acetylation
  • Histone methylation
  • Maternal low-protein diet
  • cAMP response element binding protein

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring. / Marwarha, Gurdeep; Claycombe-Larson, Kate; Schommer, Jared; Othman, Ghribi.

In: Journal of Nutritional Biochemistry, Vol. 45, 01.07.2017, p. 54-66.

Research output: Contribution to journalArticle

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