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Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat

Published online by Cambridge University Press:  09 January 2012

D. Caprau ,
M. E. Schober ,
K. Bass ,
S. O'Grady ,
X. Ke ,
B. Block ,
C. W. Callaway ,
M. Hale ,
X. Yu  and
R. A. McKnight
...Show all authors
D. Caprau*
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
M. E. Schober
Affiliation:
Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA
K. Bass
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
S. O'Grady
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
X. Ke
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
B. Block
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
C. W. Callaway
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
M. Hale
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
X. Yu
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. A. McKnight
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. P. Kesner
Affiliation:
Department of Psychology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. H. Lane
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
*
*Address for correspondence: Dr D. Caprau, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah 84132-2202, USA. (Email diana.caprau@hsc.utah.edu)
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Abstract

Exposure to intrauterine growth restriction (IUGR) is an important risk factor for impaired learning and memory, particularly in males. Although the basis of IUGR-associated learning and memory dysfunction is unknown, potential molecular participants may be insulin-like growth factor 1 (Igf1) and its receptor, IGF1r. We hypothesized that transcript levels and protein abundance of Igf1 and IGF1r in the hippocampus, a brain region critical for learning and memory, would be lower in IUGR male rats than in age-matched male controls at birth (postnatal day 0, P0), at weaning (P21) and adulthood (P120). We also hypothesized that changes in messenger Ribonucleic acid (mRNA) transcript levels and protein abundance would be associated with specific histone marks in IUGR male rats. Lastly, we hypothesized that IUGR male rats would perform poorer on tests of hippocampal function at P120. IUGR was induced by bilateral ligation of the uterine arteries in pregnant dams at embryonic day 19 (term is 21 days). Hippocampal Igf1 mRNA transcript levels and protein abundance were unchanged in IUGR male rats at P0, P21 or P120. At P0 and P120, IGF1r expression was increased in IUGR male rats. At P21, IGF1r expression was decreased in IUGR male rats. Increased IGF1r expression was associated with more histone 3 lysine 4 dimethylation (H3K4Me2) in the promoter region. In addition, IUGR male rats performed poorer on intermediate-term spatial working memory testing at P120. We speculate that altered IGF1r expression in the hippocampus of IUGR male rats may play a role in learning and memory dysfunction later in life.

Keywords

chromatin immunoprecipitation assayhistone acetylationhistone methylationIgfuteroplacental insufficiency
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 2 , April 2012 , pp. 83 - 91
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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Footnotes

†

D. Caprau and M. Schober contributed equally to this work.

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Table S1: Primers and Probes

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