Table 2.
Clinical implications of histone modifications in perinatal hypoxia ischemia studies.
| Observed effect in HI | Observed in | Other findings | Clinical implications | References |
|---|---|---|---|---|
| ↓EZH2 ↑H3K27 3me |
Rat hippocampus | ↑ Pten/Akt/mTOR pathway ↑ Autophagy |
Sevofluorane neuroprotection via ↑ EZH2 | (152–154) |
| ↓SIRT1 | Rat hippocampus and cerebral cortex | ↑ Unfolded protein response (UPR) | Melatonin neuroprotection via ↑ SIRT1 | (155) |
| ↑ SIRT1 | Mice oligodendrocyte progenitor cells | ↑ Cdk2/Rb/E2F1 pathway ↑ Oligodendrocyte progenitor cell proliferation |
↑ Sirt1 activity for oligodendrocyte recovery | |
| ↑Acetyl-Histone H3 (Ac-H3) ↑Acetyl-Histone H4 (Ac-H4) |
Rat | ↑Caspase-3 ↑Apopstosis |
HDAC activity as target of uridine neuroprotection | (156) |
| ↑Histone 3 deimination (citH3) | Mice hippocampus, cortex, striatum and piriform cortex | ↑ TNFα | PAD inhibition as therapeutic target | (157, 158) |
| ↑REST | Hippocampal CA1 | ↓GluR2 ↓AMPA and NMDA receptors ↑Excitotoxicity |
REST inhibition as therapeutic target | (159, 160) |
SYMBOLS: ↑, Upregulation; ↓, Downregulation; EZH2, Enhancer of zeste homolog 2; HI, hypoxia-ischemia; HDAC, Histone deacetylase; PAD, protein arginine deiminases; REST, RE1-Silencing Transcription factor; SIRT1, Sirtuin 1; TNFa, Tumor necrosis factor alpha.