Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Robertson, R. Meldrum; Dawson‐Scully, Ken; Andrew, R. David

doi:10.1152/jn.00724.2019

Cited by 44 publications

(63 citation statements)

References 125 publications

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“…Cold exposure, however, tends to slow and ultimately disrupt ionoregulatory mechanisms (Koštál et al, 2006; MacMillan and Sinclair, 2011a; Overgaard and MacMillan, 2017). In the insect CNS this leads to a phenomenon known as spreading depolarization (SD), which is characterized by a rapid surge in [K + ] in the extracellular space surrounding neural and glial cells (30 - 60 mM, depending on species), followed by complete silencing of the CNS (Andersen et al, 2018; Armstrong et al, 2012; Robertson et al, 2020, 2017).…”

Section: Introductionmentioning

confidence: 99%

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Cheslock

MacMillan

2020

Preprint

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Insects, like the model species Drosophila melanogaster, lose neuromuscular function and enter a state of paralysis (chill coma) at a population- and species-specific low temperature threshold that is decreased by cold acclimation. Entry into this coma is related to a spreading depolarization in the central nervous system, while recovery involves restoration of electrochemical gradients across muscle cell membranes. The Na+/K+-ATPase helps maintain ion balance and membrane potential in both the brain and hemolymph (surrounding muscles), and changes in thermal tolerance traits have therefore been hypothesized to be closely linked to variation in the expression and/or activity of this pump in multiple tissues. Here, we tested this hypothesis by measuring activity and thermal sensitivity of the Na+/K+-ATPase at the tagma-specific level (head, thorax and abdomen) in warm-(25°C) and cold-acclimated (15°C) flies by Na+/K+-ATPase activity at 15, 20, and 25°C. We relate differences in pump activity to differences in chill coma temperature, spreading depolarization temperature, and thermal dependence of muscle cell polarization. Differences in pump activity and thermal sensitivity induced by cold acclimation varied in a tissue-specific manner: While cold-acclimated flies had decreased thermal sensitivity of Na+/K+-ATPase that maintains activity at low temperatures in the thorax (mainly muscle), activity instead decreased in the heads (mainly brain). We argue that these changes may assist in maintenance of K+ homeostasis and membrane potential across muscle membranes and discuss how reduced Na+/K+-ATPase activity in the brain may counterintuitively help insects delay coma onset in the cold.

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Section: Introductionmentioning

confidence: 99%

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Cheslock

MacMillan

2020

Preprint

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“…SD events are characterized by a rapid surge in interstitial [K + ] that completely silences the CNS at a temperature closely associated with the loss of coordinated movements at the CT min and CT max [3,4,47]. However, while haemolymph hyperkalaemia appears to be detrimental for muscle viability, the SD event has been hypothesized to serve a neuroprotective function in insects [6,47]. Indeed, it has been proposed that the large shifts in interstitial ion concentrations that occur during SD could induce channel and/or spike arrest in the CNS such that the SD serves to lower metabolic demand during exposure to extreme conditions [4,48].…”

Section: Discussion (A) Stressful Cold Causes Injury and Activates Prmentioning

confidence: 99%

“…These insects enter a state of paralysis called chill coma [2] that can be reversed following rewarming. The temperature of this paralysis event and the time required to recover the ability to stand following a cold stress (chill coma recovery time; CCRT) are non-lethal and widely used measures of insect chill tolerance [3][4][5][6]. If a cold exposure is severe enough (defined depending on the species/population under study and its prior thermal history), however, chill-susceptible insects suffer from cold-induced injuries-termed chilling injury-that can be sublethal or lethal [1].…”

Section: Introductionmentioning

confidence: 99%

Hyperkalaemia, not apoptosis, accurately predicts insect chilling injury

et al. 2020

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There is a growing appreciation that insect distribution and abundance are associated with the limits of thermal tolerance, but the physiology underlying thermal tolerance remains poorly understood. Many insects, like the migratory locust ( Locusta migratoria ), suffer a loss of ion and water balance leading to hyperkalaemia (high extracellular [K + ]) in the cold that indirectly causes cell death. Cells can die in several ways under stress, and how they die is of critical importance to identifying and understanding the nature of thermal adaptation. Whether apoptotic or necrotic cell death pathways are responsible for low-temperature injury is unclear. Here, we use a caspase-3 specific assay to indirectly quantify apoptotic cell death in three locust tissues (muscle, nerves and midgut) following prolonged chilling and recovery from an injury-inducing cold exposure. Furthermore, we obtain matching measurements of injury, extracellular [K + ] and muscle caspase-3 activity in individual locusts to gain further insight into the mechanistic nature of chilling injury. We found a significant increase in muscle caspase-3 activity, but no such increase was observed in either nervous or gut tissue from the same animals, suggesting that chill injury primarily relates to muscle cell death. Levels of chilling injury measured at the whole animal level, however, were strongly correlated with the degree of haemolymph hyperkalaemia, and not apoptosis. These results support the notion that cold-induced ion balance disruption triggers cell death but also that apoptosis is not the main form of cell damage driving low-temperature injury.

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“…SD events are characterized by a rapid surge in interstitial [K + ] that completely silences the CNS at a temperature closely associated with the loss of coordinated movements at the CTmin and CTmax (4, 5, 51). However, while an increase in extracellular [K + ] in the hemolymph appears to be detrimental, the SD event has been hypothesized to serve a neuroprotective function in insects (7,51). Indeed, it has been proposed that the large shifts in interstitial ion concentrations that occur during SD (not only [K + ] changes, see (52)) could induce channel and/or spike arrest in the CNS such that the SD serves to lower metabolic demand during exposure to extreme conditions (53)(54)(55).…”

Section: The Central Nervous System Not Only Distinguishes Itself Fromentioning

confidence: 99%

“…These insects enter a state of paralysis called chill coma (2,3) that can be reversed following rewarming. The temperature of this paralysis event and the time required to recover the ability to stand following a cold stress (chill coma recovery time; CCRT) are non-lethal and widely used measures of insect chill tolerance (4)(5)(6)(7). If a cold exposure is severe enough (defined depending on the species/population under study and its prior thermal history), however, chill susceptible insects suffer from cold-induced injuries -termed chilling injury -that can be sublethal or lethal (1).…”

Section: Introductionmentioning

confidence: 99%

Hyperkalemia, not apoptosis, accurately predicts chilling injury in individual locusts

Carrington

Andersen

Brzezinski

et al. 2020

Preprint

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AbstractDuring prolonged or severe chilling, the majority of insects accrue chilling injuries that are typically quantified by scoring neuromuscular function after rewarming. In the cold, these chill susceptible insects, like the migratory locust (Locusta migratoria) suffer a loss of ion and water balance that is hypothesized to initiate cell death. Whether apoptotic or necrotic cell death pathways are responsible for this chilling injury is unclear. Here, we use a caspase-3 specific assay to indirectly quantify apoptosis in three locust tissues (muscle, nerves, and midgut) following prolonged chilling and recovery from an injury-inducing cold exposure. Furthermore, we obtain matching measurements of injury, hemolymph [K+], and muscle caspase-3 activity in individual locusts to gain further insight into mechanistic nature of chilling injury. We hypothesized that apoptotic cell death in both muscle and nerve tissue drives motor defects following cold exposure in insects, and that there would be a strong association between cold- induced injury, hyperkalemia, and muscle caspase-3 activity. We found a significant increase in muscle caspase-3 activity, but no such increase was observed in either nervous or gut tissue from the same animals, suggesting that chill injury primarily relates to apoptotic muscle cell death. However, the levels of chilling injury measured at the whole animal level prior to tissue sampling were strongly correlated with the degree of hemolymph hyperkalemia, but not apoptosis. These results support the notion that cold-induced ion balance disruption triggers cell death but also that apoptosis is not the main cell death pathway driving injury in the cold.Significance StatementTemperature has profound effects on animal fitness and sets limits to animal distribution. To understand and model insect responses to climate, we need to know how temperature sets limits to their survival. There is strong evidence that a collapse of ion and water balance occurs in insects in the cold, and it is generally held that the resulting cold injury is caused by activation of programmed cell death (apoptosis). Here, we directly test this idea and show for the first time that although the loss of ion balance is a strong predictor of individual survival outcomes, apoptosis is not the primary cause of cold-induced injury.

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Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Cited by 44 publications

References 125 publications

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Hyperkalaemia, not apoptosis, accurately predicts insect chilling injury

Hyperkalemia, not apoptosis, accurately predicts chilling injury in individual locusts

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Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Cited by 44 publications

References 125 publications

Thermal acclimation alters the roles of Na+/K+-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Thermal acclimation alters the roles of Na+/K+-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Hyperkalaemia, not apoptosis, accurately predicts insect chilling injury

Hyperkalemia, not apoptosis, accurately predicts chilling injury in individual locusts

Contact Info

Product

Resources

About

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster

Thermal acclimation alters the roles of Na⁺/K⁺-ATPase activity in a tissue-specific manner inDrosophila melanogaster