Location: Healthy Body Weight ResearchTitle: Maternal low protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring
|MARWARHA, GURDEEP - University Of North Dakota|
|SCHOMMER, JARED - University Of North Dakota|
|GHRIBI, OTHMAN - University Of North Dakota|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2017
Publication Date: 7/1/2017
Publication URL: http://handle.nal.usda.gov/10113/5667790
Citation: Marwarha, G., Larson, K.J., Schommer, J., Ghribi, O. 2017. Maternal low protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring. Journal of Nutritional Biochemistry. 45:54-66.
Interpretive Summary: We have previously determined that maternal undernutrition such as a low protein (LP) diet causes the offspring obesity with increased risk for type 2 diabetes (T2D). In addition, offspring of maternal LP diet are at risk for decreased learning and memory functions. The exact reasons for these mental disabilities in offspring fed maternal LP diet is currently not known. Therefore, we tested whether the brain-derived neurotrophic factor (BDNF), a well-known factor that controls learning and memory functions in the brain, has been altered in rat offspring whose mothers were fed a low protein (LP) diet. Results showed that a maternal LP diet caused decreases in brain tissue BDNF protein and mRNA levels in the offspring. We further tested whether other key factors that control BDNF itself were altered. Results showed that other factors that control BDNF such as the cAMP, protein kinase A (PKA) and cAMP response element binding protein (CREB), and trimethylated histones were all reduced in brains of maternal LP diet fed offspring. While future studies are necessary to determine whether actual learning and memory function defects can be detected in brains of offspring fed maternal LP diet, this study is the first to determine the impact of a maternal LP diet on brain BDNF levels.
Technical Abstract: Prenatal exposure to a maternal low protein 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 low protein (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 diet (NP) or an 8% low protein (LP) three 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 (PKA)/ 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 a LP diet.