Abstract
The Bcl-2-interacting death suppressor (Bis) protein is involved in antiapoptosis and antistress pathways. However, its roles after neonatal hypoxia-ischemia remain obscure. Therefore, we investigated the effects of Bis deletion on hippocampal cell death following neonatal hypoxia-ischemia. We transected the right common carotid artery of bis+/+ and bis-/- mice at postnatal Day 7 and subjected them to hypoxia for 35 min. Cresyl violet staining showed that hypoxia-ischemia induced progressive cell death in the hippocampi of bis+/+ mice. Moreover, Bis was expressed in astrocytes, not microglia, in sham-manipulated hippocampi of bis+/+ mice, and was markedly enhanced after hypoxia-ischemia. Immunoblotting showed that Bis expression significantly increased 3 and 7 days following hypoxia-ischemia. Unexpectedly, 7 days after hypoxia-ischemia, the number of hippocampal NeuN-positive cells was higher in the bis-/- mice than in the bis+/+ mice. We subsequently performed transcriptomic analysis and quantitative real time polymerase chain reaction to search for the underlying genes responsible for resistance to hypoxia-ischemia in the bis-/- hippocampus. These studies showed that 6 h after hypoxia-ischemia, galectin 3 and filamin C levels increased to a lesser extent in the bis-/- hippocampi compared with the bis+/+ hippocampi. Finally, our in vitro hypoxia-ischemia model, using A172 glioma cells and primary astrocytes, showed that downregulation of Bis blocked the enhanced expression of galectin 3 after oxygen-glucose deprivation. This study demonstrated that Bis was upregulated in the astrocytes after hypoxia-ischemia. In addition, we showed that hippocampal neurons are less vulnerable to hypoxia-ischemia in mice lacking Bis, possibly because of the modulation of galectin 3 induction.
Original language | English (US) |
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Pages (from-to) | 1915-1929 |
Number of pages | 15 |
Journal | GLIA |
Volume | 60 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2012 |
Keywords
- Astrocytes
- Bis (Bag3)
- Brain
- Galectin 3
- Hippocampus
- Neonatal hypoxia-ischemia
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience