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Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex
Journal article   Open access   Peer reviewed

Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex

Tate Gisslen, Kathleen Ennis, Vineet Bhandari and Raghavendra Rao
Pediatric research, v 78(5), pp 513-519
Nov 2015
DOI: https://doi.org/10.1038/pr.2015.136
PMID: 26200703
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/pr.2015.136View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Animals Animals, Newborn Blood Glucose - metabolism CD11 Antigens - metabolism Cerebral Cortex - enzymology Cerebral Cortex - pathology Disease Models, Animal Glucose Hyperglycemia - blood Hyperglycemia - chemically induced Hyperglycemia - enzymology Hyperglycemia - genetics Hyperglycemia - pathology I-kappa B Proteins - genetics I-kappa B Proteins - metabolism Insulin - blood Microglia - enzymology Microglia - pathology NF-kappa B - genetics NF-kappa B - metabolism NF-KappaB Inhibitor alpha Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism Nitric Oxide Synthase Type III - genetics Nitric Oxide Synthase Type III - metabolism Octreotide Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases - genetics Poly(ADP-ribose) Polymerases - metabolism Rats, Sprague-Dawley Recurrence RNA, Messenger - metabolism Signal Transduction Time Factors Up-Regulation
Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood. Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry. Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia. Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.

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14 citations in Web of Science
15 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#5 Gender Equality
#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Pediatrics
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