Slow death in the leopard frogRana pipiens: neurotransmitters and anoxia tolerance

Abstract

The effects of anoxia/ischemia on the mammalian brain, and the mechanisms that promote survival or neuronal failure, have been extensively studied owing to their great significance in human pathophysiology. In brief, the mammalian brain loses ATP within minutes of oxygen deprivation, with a subsequent failure of ATP-dependent ion exchangers, the loss of ionic gradients, and membrane depolarization. Depolarization then results in a cytotoxic increase in intracellular Ca 2+ concentration, the uncontrolled release of excitatory neurotransmitters to neurotoxic levels, and subsequent neuronal death (for a review, see Lutz et al., 2003). Once temperature differences are taken into account, this scenario is in fact the characteristic response of nearly all vertebrate brains, from fish to mammals (Lutz et al., 2003). A few species, however, including turtles in the genera Trachemys and Chrysemys and fish in the genus Carassius, can survive anoxia for days at 25°C and months at temperatures below 10°C (Lutz et al., 2003). These animals are able to greatly reduce brain metabolic rates to a level where energy costs are matched by anaerobic energy production; ATP levels are thus maintained and anoxic depolarization is avoided. Specific adaptations by which the brains of the anoxia-tolerant organisms survive include a reduction in membrane ion permeability (channel arrest) (Bickler et al., 2002), the release of inhibitory neurotransmitters such as GABA and alanine , and protection against the uncontrolled release of such excitotoxic compounds as glutamate and dopamine (Milton and Lutz, 1998;Milton et al., 2002).Some frog species (Rana temporaria, Rana pipiens) demonstrate an intermediate anoxia tolerance, their brains able to survive 4-5·h without oxygen at room temperature (Knickerbocker and Lutz, 2001;Lutz and Reiners, 1997) and at least 30·h without oxygen at 5°C (Hermes-Lima and Storey, 1996). This tolerance to anoxia appears to be accomplished through an overall metabolic depression, primarily via hypoperfusion of the skeletal muscle , which allows the frog to maintain ATP levels in certain organ systems. However, unlike truly anoxia-tolerant vertebrates, the frog brain does not defend ATP levels, and when energy stores reach a critical low, (approximately 35% of normoxic levels), ion homeostatic mechanisms are compromised and extracellular K + levels While frogs such as Rana temporaria are known to withstand 4-5·h anoxia at room temperature, little is known about the neurological adaptations that permit this. Previous research has shown that changes in neuroactive compounds such as glutamate and dopamine in anoxia-sensitive (mammalian) brains follow a strikingly different pattern than is observed in truly anoxia-tolerant vertebrates such as the freshwater turtle. The present study measured changes in the levels of whole brain and extracellular amino acids, and extracellular dopamine, in the normoxic and 3-4·h anoxic frog Rana pipiens, in order to determine whether their neurotransmitter responses resemble the anoxia-vu...

Size‐ and temperature‐independence of minimum life‐supporting metabolic rates

“…For organisms tolerating hours and days of anoxia it has been long known, although never emphasized, that metabolic rates measured during anoxia reflect processes of biochemical degradation, such as tissue autolysis (Shick, de Zwaan & de Bont 1983). Only recently has it been explicitly recognized that anoxic existence can represent gradual death rather than sustainable maintenance: the slower the processes of degradation, the longer the survival time (Knickerbocker & Lutz 2001; Milton, Manuel & Lutz 2003). These observations, and the data that are presented below, justify the application of the proposed notion of abandoned metabolic control to describe obligate aerobes under anoxic conditions.…”

Physiological Diversity in Insects: Ecological and Evolutionary Contexts

“…The value of θ, or the form of the relationship between number of days remaining until N max and W T , has a significant influence on the likelihood that freezing tolerance will be favoured, but has not been explored at all. If frozen individuals are largely anoxic (Storey and Storey, 1996;Morin et al, 2005), then duration of survival is likely to be a function not of energy stores, but rather of the extent of damage owing to chaotic biochemical reactions (Knickerbocker and Lutz, 2001;Milton et al, 2003a;Makarieva et al, 2006). Anoxic organisms die after the cumulative energetic yield of chaotic anoxic biochemical processes has passed c. 70-100 kJ (kg dry mass) −1 , which means that the more effectively an organism can suppress the accumulation of disorder, the longer it will survive (Fig.…”

Small Non-coding RNA Expression and Vertebrate Anoxia Tolerance

“…Since the leopard frog and the epaulette shark are less anoxia tolerant than the carp and turtle, they represent intermediates on the spectrum between highly anoxia-tolerant and anoxia-sensitive species ( Bickler and Buck, 2007 ). While the habitats and physiology of each species vary, all of these species employ profound metabolic depression in order to survive anoxia ( Lutz et al, 1996 ; Milton et al, 2003 ; Nilsson and Renshaw, 2004 ), and therefore, may employ similar mechanisms at the cellular and genetic levels, such as with small ncRNAs.…”