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IUGR disrupts the PPARγ-Setd8-H4K20me(1) and Wnt signaling pathways in the juvenile rat hippocampus. Int J Dev Neurosci 2014 Nov;38:59-67

Date

08/12/2014

Pubmed ID

25107645

Pubmed Central ID

PMC4268161

DOI

10.1016/j.ijdevneu.2014.07.008

Scopus ID

2-s2.0-84906701300   10 Citations

Abstract

Intrauterine growth restriction (IUGR) programs neurodevelopmental impairment and long-term neurological morbidities. Neurological morbidities in IUGR infants are correlated with changes hippocampal volume. We previously demonstrated that IUGR alters hippocampal cellular composition in both neonatal and juvenile rat pups in association with altered hippocampal gene expression and epigenetic determinants. PPARγ signaling is important for neurodevelopment as well as epigenetic integrity in the brain via the PPARγ-Setd8-H4K20me(1) axis and Wnt signaling. We hypothesized that IUGR would decrease expression of PPARγ, Setd8, and H4K20me(1) in juvenile rat hippocampus. We further hypothesized that reduced PPARγ-Setd8-H4K20me(1) would be associated with reduced Wnt signaling genes Wnt3a and β-catenin, and wnt target gene Axin2. To test our hypothesis we used a rat model of uteroplacental insufficiency-induced IUGR. We demonstrated that PPARγ localizes to oligodendrocytes, neurons and astrocytes within the juvenile rat hippocampus. We also demonstrated that IUGR reduces levels of PPARγ, Setd8 and H4K20me(1) in male and female juvenile rat hippocampus in conjunction with reduced Wnt signaling components in only male rats. We speculate that reduced PPARγ and Wnt signaling may contribute to altered hippocampal cellular composition which, in turn, may contribute to impaired neurodevelopment and subsequent neurocognitive impairment in IUGR offspring.

Author List

Ke X, Xing B, Yu B, Yu X, Majnik A, Cohen S, Lane R, Joss-Moore L

Author

Susan Cohen MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actins
Animals
Animals, Newborn
Body Weight
Disease Models, Animal
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Hippocampus
Histone-Lysine N-Methyltransferase
Histones
Male
PPAR gamma
Phosphopyruvate Hydratase
RNA, Messenger
Rats
Sex Factors
Wnt Signaling Pathway
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