RGD Reference Report - Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain. - Rat Genome Database

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Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain.

Authors: Lee, HM  Greeley GH, JR  Englander, EW 
Citation: Lee HM, etal., Free Radic Biol Med. 2008 Mar 1;44(5):807-14. Epub 2007 Nov 21.
RGD ID: 2302401
Pubmed: PMID:18078825   (View Abstract at PubMed)
PMCID: PMC2730834   (View Article at PubMed Central)
DOI: DOI:10.1016/j.freeradbiomed.2007.11.005   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to hypoxia  IEP 2302401 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nrf1  (nuclear respiratory factor 1)


Additional Information