Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain

Heung M. Lee, George H. Greeley, Ella Englander

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The effects of placental insufficiency and preterm birth on neurodevelopment can be modeled in experimental settings of neonatal hypoxia in rodents. Here, rat pups were reared in reduced oxygen (9.5%) for 11 days, starting on postnatal day 3 (P3). This led to a significant reduction in brain and body weight gain in hypoxic pups compared to age-matched normoxia-reared controls, plausibly reflecting an inability to fulfill the energetic needs of normal growth and development. Adaptive processes designed to augment energetic capacity in eukaryotes include stimulation of mitochondrial biogenesis. We show that after 11 days of sustained hypoxia, the levels of nuclear respiratory factor-1 and mitochondrial transcription factor A are elevated and the content of mitochondrial DNA (mtDNA) is greater in the hypoxic P14 pup brain compared to normoxic conditions. Corresponding immunohistochemical analyses reveal increased density of mtDNA in large cortical neurons. In contrast, no changes in mtDNA content are observed in the brain of pups reared for 24 h (P3-P4) under hypoxic conditions. Together, these data suggest that prolonged inadequate oxygenation may trigger a compensatory increase in neuronal mitochondrial DNA content to partially mitigate compromised energy homeostasis and reduced energetic capacity in the developing hypoxic brain.

Original languageEnglish (US)
Pages (from-to)807-814
Number of pages8
JournalFree Radical Biology and Medicine
Volume44
Issue number5
DOIs
StatePublished - Mar 1 2008

Fingerprint

Mitochondrial DNA
Rats
Brain
Nuclear Respiratory Factor 1
Placental Insufficiency
Oxygenation
Premature Birth
Organelle Biogenesis
Eukaryota
Growth and Development
Neurons
Weight Gain
Rodentia
Homeostasis
Body Weight
Oxygen
Hypoxia

Keywords

  • Caloric restriction
  • Free radicals
  • Mild hypoxia
  • Mitochondrial DNA
  • Neonate
  • Neurodevelopment
  • Nitrotyrosine
  • Nuclear respiratory factor-1

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain. / Lee, Heung M.; Greeley, George H.; Englander, Ella.

In: Free Radical Biology and Medicine, Vol. 44, No. 5, 01.03.2008, p. 807-814.

Research output: Contribution to journalArticle

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