Abstract
Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection.
Highlights
Neural function is critically dependent on maintaining cellular ion homeostasis which in turn is dependent on an adequate energy supply
Loss of ion homeostasis with consequent depolarization of neurons and glia occurs in response to anoxia and in healthy tissue complete recovery is possible on return to normoxia within species-specific time limits
The utility of Drosophila for insight into vertebrate brain function is well-established [35] and the fly has long been used as a model system for the dissection of the genetic basis of tolerance and susceptibility to hypoxia [1,36]
Summary
Neural function is critically dependent on maintaining cellular ion homeostasis which in turn is dependent on an adequate energy supply. Following traumatic brain injury PIDs originate within the injured cortex and propagate outwards, turning into repetitive SD events in the surrounding penumbra [7] and increasing the volume of dead tissue [15,17]. This increase occurs when energetic costs associated with repetitive SD [18] outstrip the limited energy resources of the metabolically compromised penumbra [19]. Cellular mechanisms that modulate repetitive AD or PID and their effect on ion homeostasis are poorly understood
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