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Chronological changes and effects of AMP-activated kinase in the hippocampal CA1 region after transient forebrain ischemia in gerbils.

AbstractOBJECTIVES:
Adenosine monophosphate-activated kinase (AMPK) is an energy-specific sensor within the central nervous system. In this study, we observed AMPK and its phosphorylated form (pAMPK) in the hippocampal CA1 region after 5 minutes of transient forebrain ischemia. In addition, we also investigated the effects of Compound C, an AMPK inhibitor, against ischemic damage in gerbils.
METHODS:
Adenosine monophosphate-activated kinase and pAMPK immunoreactivity was observed in the hippocampal CA1 region at various time points after ischemia and Compound C was intraperitoneally administered to gerbils immediately after reperfusion and the animals were sacrificed at 5 days after ischemia/reperfusion.
RESULTS:
Adenosine monophosphate-activated kinase immunoreactivity was transiently increased in the hippocampal CA1 region 1-2 days after ischemia/reperfusion, while AMPK immunoreactivity was almost undetectable in the stratum pyramidale of the CA1 region 4-7 days after ischemia/reperfusion. The administration of Compound C caused a dose-dependent decrease in the ischemia-induced hyperactive behavior, the depletion of ATP, and lactate accumulation in the hippocampal CA1 region within 24 hours after ischemia/reperfusion. In addition, the administration of Compound C decreased reactive gliosis (astrocytes and microglia) and increased the number of cresyl violet-positive neurons when compared to the vehicle-treated group at 5 days post-ischemia/reperfusion.
CONCLUSION:
These results suggest that AMPK is transiently phosphorylated following forebrain ischemia in the hippocampal CA1 region and inhibition of AMPK has neuroprotective effects against ischemic damage through the reduction of ATP depletion and lactate accumulation in the hippocampal CA1 region.
AuthorsHan Ga Wi Nam, Woosuk Kim, Dae Young Yoo, Jung Hoon Choi, Moo-Ho Won, In Koo Hwang, Je Hoon Jeong, Hyung Sik Hwang, Seung-Myung Moon
JournalNeurological research (Neurol Res) Vol. 35 Issue 4 Pg. 395-405 (May 2013) ISSN: 1743-1328 [Electronic] England
PMID23540408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Pyrazoles
  • Pyrimidines
  • dorsomorphin
  • Adenylate Kinase
Topics
  • Adenylate Kinase (metabolism)
  • Animals
  • CA1 Region, Hippocampal (drug effects, enzymology)
  • Enzyme Inhibitors (pharmacology)
  • Gerbillinae
  • Immunohistochemistry
  • Ischemic Attack, Transient (enzymology)
  • Male
  • Neuroprotective Agents (pharmacology)
  • Prosencephalon (blood supply)
  • Pyrazoles (pharmacology)
  • Pyrimidines (pharmacology)
  • Time

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