1. ¹Alaskan Basic Neuroscience Program, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, USA
2. ²Department of Anesthesia, University of California San Francisco, San Francisco, California, USA

Correspondence: Dr KL Drew, Alaskan Basic Neuroscience Program, Institute of Arctic Biology, University of Alaska Fairbanks, PO Box 757000, Fairbanks, AK 99775-7000, USA. E-mail: ffkld@uaf.edu

Received 1 October 2007; Revised 24 January 2008; Accepted 27 February 2008; Published online 9 April 2008.

Abstract

Oxygen–glucose deprivation (OGD) initiates a cascade of intracellular responses that culminates in cell death in sensitive species. Neurons from Arctic ground squirrels (AGS), a hibernating species, tolerate OGD in vitro and global ischemia in vivo independent of temperature or torpor. Regulation of energy stores and activation of mitogen-activated protein kinase (MAPK) signaling pathways can regulate neuronal survival. We used acute hippocampal slices to investigate the role of ATP stores and extracellular signal-regulated kinase (ERK)1/2 and Jun NH₂-terminal kinase (JNK) MAPKs in promoting survival. Acute hippocampal slices from AGS tolerated 30 mins of OGD and showed a small but significant increase in cell death with 2 h OGD at 37°C. This tolerance is independent of hibernation state or season. Neurons from AGS survive OGD despite rapid ATP depletion by 3 mins in interbout euthermic AGS and 10 mins in hibernating AGS. Oxygen–glucose deprivation does not induce JNK activation in AGS and baseline ERK1/2 and JNK activation is maintained even after drastic depletion of ATP. Surprisingly, inhibition of ERK1/2 or JNK during OGD had no effect on survival, whereas inhibition of JNK increased cell death during normoxia. Thus, protective mechanisms promoting tolerance to OGD by AGS are downstream from ATP loss and are independent of hibernation state or season.