We observed chronological changes in the mitochondrial-specific antioxidant enzymes peroxiredoxin 3 (Prx3) and thioredoxin 2 (Trx2) and their neuroprotective effects in the hippocampal CA1 region after 5 min of transient cerebral ischemia in gerbils. In the sham-operated group, weak Prx3 and Trx2 immunoreactivity was detected in the stratum pyramidale. Prx3 immunoreactivity was increased in pyramidal neurons and expressed in microglia 1 and 3 days, respectively, after ischemia/reperfusion (I/R). Trx2 immunoreactivity in pyramidal neurons increased 30 min and 1 day after I/R and decreased 6 h after I/R. Trx2 immunoreaction was expressed in astrocytes at 3 days postischemia. The intraventricular administration of Prx3 or Prx3/Trx2 (16 μg/20 μl, icv) using an osmotic pump significantly reduced ischemia-induced hyperactivity in a spontaneous motor test and protected CA1 pyramidal neurons from the ischemic damage. In addition, the activation of astrocytes and microglia was decreased in the ischemic CA1 region after Prx3/Trx2 treatment. In addition, treatment with Prx3 or Prx3/Trx2 significantly reduced lipid peroxidation and the release of cytochrome c from mitochondria and cytoplasm in the ischemic CA1 region. These results suggest that changes in the expression of Prx3 and Trx2 in the hippocampal CA1 region after I/R may be associated with the delayed neuronal death of CA1 pyramidal cells induced by transient cerebral ischemia, and that treatment with Prx3 or Prx3/Trx2 in ischemic brains shows a potent neuroprotective effect against ischemic damage by reducing lipid peroxidation and mitochondrial-mediated apoptosis by I/R.
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|Publication status||Published - 2010 May|
Bibliographical noteFunding Information:
The authors thank Mr. Suek Han, Mr. Seung Uk Lee, and Ms. Hyun Sook Kim for their technical help in this study. This study was supported by the MRC program MOST/KOSEF ( R13-2005-022-01002-0 ) and by a grant ( 2009K001290 ) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, the Republic of Korea .
All Science Journal Classification (ASJC) codes
- Physiology (medical)