Granulocyte Colony-Stimulating Factor Alleviates Bacterial-Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification

Yung Ning Yang, Yu Tsun Su, Pei Ling Wu, Chun Hwa Yang, Yu Chen S.H. Yang, Jau Ling Suen, San Nan Yang

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Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-κB phosphorylation and trimethylated H3K4 in the TNFA gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.

Original languageEnglish
Article number9797146
JournalOxidative Medicine and Cellular Longevity
Publication statusPublished - Jan 1 2018


ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

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