title: IUGR disrupts the PPARγ-Setd8-H4K20me(1) and Wnt signaling pathways in the juvenile rat hippocampus.
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.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
authors.forename: Xingrao
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT 84158, United States.
authors.forename: Bohan
authors.initials: B
authors.lastname: Xing
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT 84158, United States.
authors.forename: Baifeng
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT 84158, United States.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
authors.forename: Amber
authors.initials: A
authors.lastname: Majnik
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Lane
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT 84158, United States. Electronic address: lisa.joss-moore@hsc.utah.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Joss-Moore
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D012737:Sex Factors; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000199:Actins; D006657:Histones; D047495:PPAR gamma; D012333:RNA, Messenger; D011495:Histone-Lysine N-Methyltransferase; D010751:Phosphopyruvate Hydratase
keywords: Brain development; Epigenetics; Intrauterine growth restriction; PPARγ
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