Persistent Tolerance to Oxygen and Nutrient Deprivation and <i>N</i>-methyl-D-Aspartate in Cultured Hippocampal Slices from Hibernating Arctic Ground Squirrel

Ross, Austin P.; Christian, Sherri L.; Zhao, Hongbin; Drew, Kelly L.

doi:10.1038/sj.jcbfm.9600271

Cited by 54 publications

(66 citation statements)

References 43 publications

(46 reference statements)

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“…A possible adaptive function for the loss of synapses is neural protection from reperfusion injury with arousal (Ross et al, 2006). However, there are likely costs to this form of plasticity as well, including deficits in some forms of memory that were acquired prehibernation (Mateo and Johnston, 2000;Millesi et al, 2001) and energy costs of repeatedly rebuilding dendritic arbors and spines.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitous and Temperature-Dependent Neural Plasticity in Hibernators

Ohe¹,

Darian‐Smith²,

Garner³

et al. 2006

J. Neurosci.

136

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Hibernating mammals are remarkable for surviving near-freezing brain temperatures and near cessation of neural activity for a week or more at a time. This extreme physiological state is associated with dendritic and synaptic changes in hippocampal neurons. Here, we investigate whether these changes are a ubiquitous phenomenon throughout the brain that is driven by temperature. We iontophoretically injected Lucifer yellow into several types of neurons in fixed slices from hibernating ground squirrels. We analyzed neuronal microstructure from animals at several stages of torpor at two different ambient temperatures, and during the summer. We show that neuronal cell bodies, dendrites, and spines from several cell types in hibernating ground squirrels retract on entry into torpor, change little over the course of several days, and then regrow during the 2 h return to euthermia. Similar structural changes take place in neurons from the hippocampus, cortex, and thalamus, suggesting a global phenomenon. Investigation of neural microstructure from groups of animals hibernating at different ambient temperatures revealed that there is a linear relationship between neural retraction and minimum body temperature. Despite significant temperature-dependent differences in extent of retraction during torpor, recovery reaches the same final values of cell body area, dendritic arbor complexity, and spine density. This study demonstrates large-scale and seemingly ubiquitous neural plasticity in the ground squirrel brain during torpor. It also defines a temperature-driven model of dramatic neural plasticity, which provides a unique opportunity to explore mechanisms of large-scale regrowth in adult mammals, and the effects of remodeling on learning and memory.

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Section: Discussionmentioning

confidence: 99%

Ubiquitous and Temperature-Dependent Neural Plasticity in Hibernators

Ohe¹,

Darian‐Smith²,

Garner³

et al. 2006

J. Neurosci.

136

View full text Add to dashboard Cite

show abstract

“…During the torpor state of hibernation, the metabolic rate can be reduced to as low as 2% of baseline level (Geiser, 1988), while CBF can be reduced to 11% of baseline (Frerichs et al, 1994) without causing injury. Hibernation provides ischemic tolerance even in hippocampal slices obtained from hibernating animals (Ross et al, 2006). Neuroprotection by massive metabolic suppression under a controlled torpid state could be highly valuable to translational stroke research (Drew et al, 2007;Fisher and Henninger, 2007;Frerichs, 1999;Lee and Hallenbeck, 2006).…”

Section: Metabolic Suppression and Energy Deliverymentioning

confidence: 99%

The Continued Promise of Neuroprotection for Acute Stroke Treatment

Liu¹,

Levine²

2008

Journal of Experimental Stroke and Translational Medicine

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Stroke is the second leading cause of death. However, effective pharmocologic treatment options are still extremely limited and applicable to only a small fraction of patents. The translational failure in finding an effective neuroprotectant for ischemic strokes has generated an active discussion in this field. One focus has been on validating systems for testing neuroprotectants. This review discusses some fundamental issues in experimental stroke that are worthy of further exploration. We begin with a general review of the current status of experimental stroke research and then move on to a discussion of the determining factors and processes that control and differentiate the fate of ischemic ischemic cells and tissue. We propose several strategies of neuroprotection for ischemic strokes with an emphasis on manipulating cellular energy state.

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“…In vitro acute hippocampal slices from hibernating 13-lined ground squirrels tolerate oxygen-glucose deprivation (OGD) better than euthermic squirrels or rat, and as temperature is decreased protection from OGD is also seen in tissue from euthermic animals . In contrast, in short-term culture at 371C, hippocampal slices from hibernating and euthermic Arctic ground squirrels (AGS, Spermophilus parryii) tolerated modeled ischemia equally well (Ross et al, 2006). In support of this profound in vitro tolerance, euthermic AGS also tolerate 8 mins of global cerebral ischemia in vivo without loss of CA1 neurons (Dave et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Arctic Ground Squirrel (Spermophilus Parryii) Hippocampal Neurons Tolerate Prolonged Oxygen—Glucose Deprivation and Maintain Baseline ERK1/2 and JNK Activation Despite Drastic ATP Loss

Christian

Ross

Zhao

et al. 2008

J Cereb Blood Flow Metab

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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 NH 2 -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 371C. 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.

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Persistent Tolerance to Oxygen and Nutrient Deprivation and N-methyl-D-Aspartate in Cultured Hippocampal Slices from Hibernating Arctic Ground Squirrel

Cited by 54 publications

References 43 publications

Ubiquitous and Temperature-Dependent Neural Plasticity in Hibernators

Ubiquitous and Temperature-Dependent Neural Plasticity in Hibernators

The Continued Promise of Neuroprotection for Acute Stroke Treatment

Arctic Ground Squirrel (Spermophilus Parryii) Hippocampal Neurons Tolerate Prolonged Oxygen—Glucose Deprivation and Maintain Baseline ERK1/2 and JNK Activation Despite Drastic ATP Loss

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