Hypoxic survival strategies in two fishes: extreme anoxia tolerance in the North European crucian carp and natural hypoxic preconditioning in a coral-reef shark
1 Department of Molecular Biosciences, University of Oslo, PO Box 1041,
NO-0316 Oslo, Norway
2 School of Physiotherapy and Exercise Science, Griffith University, PMB 50
Gold Coast, Queensland 9726, Australia
* Author for correspondence (e-mail: g.e.nilsson{at}bio.uio.no)
Accepted 12 March 2004
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Summary |
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The crucian carp (Carassius carassius) is of particular interest because of its extreme anoxia tolerance. During the long North European winter, it survives for months in completely oxygen-deprived freshwater habitats. The crucian carp also tolerates a few days of anoxia at room temperature and, unlike anoxia-tolerant freshwater turtles, it is still physically active in anoxia. Moreover, the crucian carp does not appear to reduce neuronal ion permeability during anoxia and may primarily rely on more subtle neuromodulatory mechanisms for anoxic metabolic depression.
The epaulette shark (Hemiscyllium ocellatum) is a tropical marine vertebrate. It lives on shallow reef platforms that repeatedly become cut off from the ocean during periods of low tides. During nocturnal low tides, the water [O2] can fall by 80% due to respiration of the coral and associated organisms. Since the tides become lower and lower over a period of a few days, the hypoxic exposure during subsequent low tides will become progressively longer and more severe. Thus, this shark is under a natural hypoxic preconditioning regimen. Interestingly, hypoxic preconditioning lowers its metabolic rate and its critical PO2. Moreover, repeated anoxia appears to stimulate metabolic depression in an adenosine-dependent way.
Key words: anoxia, hypoxia, ischemia, Carassius, Hemiscyllium, coral reef, GABA, glutamate
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Introduction |
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Consequently, one may expect that hypoxia tolerance is more likely to
evolve among aquatic vertebrates and, indeed, this seems to be the case. In
the waters of the Amazon basin, where hypoxia is a common phenomenon, several
fishes have been found to show a considerable hypoxia tolerance
(Val et al., 1998), and, just
recently, it was found that hypoxia tolerance is widespread among fishes
living on coral reefs probably the most biodiverse marine habitat
(Nilsson and Östlund-Nilsson,
2004
). Clarifying the mechanisms that have evolved to allow fishes
to survive with little or no oxygen may offer new insight into the challenges
posed by hypoxia and could point to possible ways of counteracting hypoxic
damage. Such knowledge may also be applicable to vertebrates, such as humans,
that normally show a very limited hypoxia tolerance.
The animals with the best-developed tolerance to anoxia can respond to a
dramatic decline in ambient oxygen by rapidly and reversibly reprogramming
their metabolism to adjust glycolysis and ATP consumption in a highly
coordinated manner (Fig. 1). In
this way, ATP levels are defended and the catastrophic consequences of a
drastic fall in cellular energy status are avoided (see
Lutz et al., 2003 for a
review).
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In the present review, we summarise what we presently know about two hypoxia-tolerant fishes that are both able to defend their brain ATP levels when faced with a partial, or even total, lack of oxygen. One is the crucian carp (Carassius carassius L.), which is possibly the most anoxia-tolerant vertebrate there is, in close competition with some freshwater turtles. It may survive several months of complete anoxia at temperatures close to 0°C and it tolerates a day or two of anoxia at room temperature. Unlike the turtles, the crucian carp survives anoxia in an active, rather than comatose, state.
The second part of the review focuses on the epaulette shark (Hemiscyllium ocellatum Bonnaterre). This animal appears to be more hypoxia tolerant than any other cartilaginous fish, even if its tolerance is relatively modest compared with that of the crucian carp. Its hypoxia tolerance is of special interest because it has evolved at the high temperature of a tropical coral reef (close to 30°C). Moreover, tidal changes in the water level in its coral habitat result in periods of progressively more severe hypoxia that can be regarded as a natural preconditioning regimen. Indeed, repeated hypoxia exposure appears to improve its hypoxia tolerance.
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The crucian carp |
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Even more impressive may be the ability of the crucian carp to change the
morphology of its gills to increase the respiratory surface area when exposed
to hypoxia. It is the only adult vertebrate known to have this ability. Its
gill lamellae (the respiratory units of fish) become protruding after 7 days
in hypoxic waters due to an apoptotic death of cells that cover much of the
lamellar surface during normoxia (Sollid
et al., 2003).
In sharp contrast to the anoxic turtle (Trachemys scripta), which
shows profound peripheral vasoconstriction, blunted autonomic control and 80%
decreases in heart rate and cardiac output (Hicks and Farrell,
2000a,b
;
Stecyk et al., 2004
), recent
data reveal that the crucian carp maintains all these functions, and also
ventilation, at normal levels even after several days in anoxia (J. A. W.
Stecyk, K.-O. Stensløkken, A. P. Farrell and G. E. Nilsson,
unpublished). This suggests that being active in anoxia demands an active
circulatory system for shuttling glycolytic substrates and end products.
Finally, it should be mentioned that protein synthesis in the crucian carp
is drastically downregulated (by 5095%) during anoxia in organs such as
muscle and liver, where this process constitutes a major part of the energy
budget (Smith et al.,
1996).
Glycolytic adaptations to anoxia
Even if the water is totally devoid of oxygen, the crucian carp will
manage. As mentioned above, it can survive for several months in anoxia at
freezing winter temperatures and for 12 days at room temperature.
Experiments at 8°C, where the crucian carp survives for a little more than
two weeks, have indicated that the only factor that eventually limits its
anoxic survival time is the total exhaustion of its glycogen store
(Nilsson, 1990). The liver
glycogen store of crucian carp is the largest of any vertebrate studied. In
the winter, 30% of the liver wet mass is glycogen and 15% of the fish is liver
(Hyvärinen et al., 1985
).
The crucian carp keeps this enormous glycogen reserve for good reasons. During
anoxia, glucose is the only cellular fuel available, and the crucian carp
utilizes a wasteful glycolytic strategy to avoid lactate self-poisoning. It
produces ethanol that is released into the water (see
Van Waarde, 1991
for a
review). The wastefulness of this strategy is, of course, that a high-energy
carbohydrate is lost forever.
To reduce the rate of lactate production to a minimum, the anoxia-tolerant
freshwater turtle has to reduce its metabolism to an absolute minimum during
anoxia, rendering it comatose. Still, the turtle may end up with a blood
lactate level around 200 mmol l1 after a winter of anoxic
submergence (Ultsch and Jackson,
1982). The ethanol-producing strategy appears to give the crucian
carp an advantage over freshwater turtles: it can survive anoxia in an active
state, still swimming around (Nilsson et
al., 1993
). This should make it able to seek out oxygen in the
spring. The only option for the comatose turtle is to wait to be reached by
oxygen (Lutz and Nilsson,
1997
). In light of the slow rate by which oxygen diffuses, this
could make a considerable difference to the length of time the animals have to
remain anoxic.
The anoxic crucian carp brain metabolic modulation rather than shutdown
A consequence of surviving anoxia in an active state is, of course, that
the crucian carp has to survive anoxia with the brain turned on
(Nilsson, 2001). Both turtles
and crucian carp show adenosine-mediated increases in brain blood flow in
response to anoxia, probably aimed at increasing glucose delivery to the brain
(and removing waste products). However, unlike the turtle, which only shows a
temporary increase in brain blood flow as an immediate emergency response to
anoxia (Hylland et al., 1994
),
the crucian carp brain maintains this state during the whole anoxic period
(Nilsson et al., 1994
).
Surviving anoxia in an active state should put a limit to the degree of
metabolic depression that can be attained. Indeed, at the whole-body level,
the degree of metabolic depression displayed by Carassius is much
less than that shown by freshwater turtles. In anoxia, these fish reduce their
body heat production to about one-third
(Van Waversveld et al., 1989),
compared with one-tenth in turtles
(Jackson, 1968
). The crucian
carp brain appears to be at least partially metabolically depressed in anoxia.
Microcalorimetric measurements of heat production of crucian carp brain slices
(telencephalon) indicate that there is at least a 3040% reduction in
ATP turnover during anoxia, but this reduction is not large enough to avoid an
increase in glycolytic rate (Pasteur effect;
Johansson et al., 1995
). By
contrast, there are clear indications of a glycolytic downregulation in the
anoxic turtle brain (Duncan and Storey,
1991
). Also, other studies indicate that the central nervous
system (CNS) of Carassius is working at a reduced level in anoxia.
The activity of the auditory nerve of goldfish is strongly suppressed during
anoxia (Suzue et al., 1987
). A
study on crucian carp indicates that anoxia makes it temporarily blind, since
the response of the visual system to a flash of light (evoked potentials in
retina and optic tectum) virtually disappears
(Johansson et al., 1997
). With
regard to both hearing and vision, the changes seen in anoxia are reversible,
suggesting that they are orderly orchestrated downregulations aimed at saving
energy.
However, compared with being comatose, like the turtle, turning off hearing
and vision seem like minor adjustments when faced with oxygen deprivation.
This is also reflected in the mechanisms utilized by turtles, on the one hand,
and crucian carp, on the other, in downregulating nervous function in anoxia.
In turtles, there is now strong experimental evidence for `channel arrest'
an anoxia-induced downregulation of the permeability of various
neuronal ion channels (see Lutz et al.,
2003 for a review). The ions involved include K+,
Na+ and Ca2+. Experimental studies examining the
possibility of reduced neural K+ or Ca2+ permeability
during anoxia have so far failed to detect any such changes in the crucian
carp (Johansson and Nilsson,
1995
; Nilsson,
2001
), indicating that this fish relies on other mechanisms for
metabolic depression.
Also, the way brain protein synthesis is affected by anoxia differs greatly
between crucian carp and turtles, probably reflecting the divergent survival
strategies. In crucian carp, brain protein synthesis is maintained during
anoxia (Smith et al., 1996)
while in freshwater turtles it is virtually stopped
(Fraser et al., 2001
).
Neurotransmitters and neuromodulators: first and second lines of defence
It is tempting to suggest that channel arrest and a stop in protein
synthesis are much too drastic strategies for suppressing nervous activity and
ATP use in an animal that retains activity during anoxia. Instead, the crucian
carp may be relying on neurotransmitters and neuromodulators to suppress its
CNS energy use. Indeed, microdialysis measurements have shown that the
extracellular level of -amino butyric acid (GABA), the major inhibitory
transmitter in the brain, rises in the brain (telencephalon) of anoxic crucian
carp (Fig. 2A),while
extracellular [glutamate] remains low (Fig.
2B; Hylland and Nilsson,
1999
). This also occurs in anoxic turtles, which show an 80-fold
increase in extracellular GABA (Nilsson
and Lutz, 1991
). Interestingly, the GABA release in the crucian
carp brain is much more modest. On average, the extracellular GABA level is
doubled in crucian carp telencephalon after 5 h of anoxia at 10°C
(Fig. 2A). The rise also shows
considerable individual variation, which may suggest that it is tuned
according to individual needs.
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An interesting finding was that the potential for GABA release in the
crucian carp telencephalon appears to be much higher than that for glutamate.
When the brain tissue surrounding the microdialysis probe was depolarized by
running a high [K+] Ringer through the probe, the extracellular
GABA level rose 14 times, while that of glutamate barely doubled
(Fig. 2A,B). Moreover, when the
crucian carp neural ATP levels were forced to plummet, by superfusing the
brain with the glycolytic inhibitor iodoacetate (IAA), exposing the fish to
anoxia, the resultant increase in extracellular [GABA] was both faster and
more massive (a 10-fold rise after 30 min) than that of glutamate (a 3-fold
rise after 2 h) (Fig. 2C,D;
Hylland and Nilsson, 1999).
These results suggest that the anoxic crucian carp has a second line of
defence. If the brain, or parts of it, experiences energy deficiency during
anoxia, a major GABA release will be initiated, which could cause a neuronal
depression large enough to restore the ATP levels. By contrast, the release of
glutamate in the energy-depleted brain is delayed and relatively modest, which
should be of importance in light of the fact that glutamate, the major
excitatory neurotransmitter in the brain, becomes a deadly excitotoxin in the
anoxic brain of anoxia-intolerant animals. Interestingly, one class of
glutamate receptors, the group II metabotropic glutamate receptors, appears to
be involved in attenuating the effects of anoxia in the goldfish brain
(Poli et al., 2003
). These
could be particularly important in the goldfish, which does not tolerate
anoxia quite as well as the crucian carp, probably a side effect of hundreds
of years of domestication. Goldfish often show falling brain ATP levels in
anoxia (Van Ginneken et al.,
1996
) and may suffer anoxia-induced neuronal apoptosis
(Poli et al., 2003
). Other
parts of a second line of defence found in the goldfish involves the anoxic
upregulation of antioxidant enzymes such as glutathione peroxidase in response
to lipid peroxidation during reoxygenation
(Lushchak et al., 2001
).
Also, adenosine appears to play a role in metabolic depression in anoxic
Carassius. Adenosine has been shown to suppress
K+-stimulated Ca2+-dependent glutamate release in
goldfish cerebellar slices (Rosati et al.,
1995). Moreover, blocking adenosine receptors in anoxic crucian
carp causes a 3-fold increase in the rate of ethanol release to the water,
suggesting a major involvement of adenosine in metabolic depression
(Nilsson, 1991
). So far, an
increase in extracellular [adenosine] has not been directly detected in the
anoxic crucian carp brain, although superfusing it with IAA causes
extracellular [adenosine] to increase
50 times (P. Hylland and G. E.
Nilsson, unpublished). By contrast, in the anoxic brain of turtles, the
extracellular adenosine level can rise 10-fold
(Nilsson and Lutz, 1992
). It
is possible that, as with GABA, the release of adenosine in anoxic crucian
carp brain is much more modest and more variable than in the turtle, being
used to modulate the neuronal metabolic rate rather than to create a deep and
general metabolic depression.
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The epaulette shark |
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Hypoxia tolerance has been studied in the epaulette shark inhabiting the
reef platform surrounding Heron Island a small and low coral cay
situated close to the southern end of the Great Barrier Reef. At nocturnal low
tides, the water on the huge (3x10 km) reef platform becomes cut
off from the surrounding ocean, essentially forming a very large tide pool.
When this happens on calm nights with little water movements, the respiration
of the coral and all associated organisms can cause the water [O2]
to fall below 18% of air saturation
(Routley et al., 2002
).
General physiological responses to hypoxia
Like the crucian carp, the hypoxic epaulette shark maintains its ability to
move, at least initially, during hypoxia or anoxia. However, as pointed out
below, an extended period of anoxia may drive the epaulette shark into a
deeper metabolic depression where it loses much of its responsiveness to
external stimuli. On the respiratory level, there is a change in the gill
perfusion pattern in the epaulette shark that may serve to give improved
oxygen uptake (K.-O. Stensløkken, L. Sundin, G. E. Nilsson and G. M. C.
Renshaw, unpublished observations) and ventilatory frequency increases to
achieve short-term tolerance to moderate hypoxia
(Routley et al., 2002).
Interestingly, several other basic physiological responses of the epaulette
shark to hypoxia appear to be different from those of other vertebrates,
including those that readily tolerate hypoxia. Thus, unlike many other
animals, the epaulette shark does not increase blood glucose levels or
haematocrit during acute or chronic hypoxia. Indeed, its haematocrit is quite
low (1015%; Routley et al.,
2002
). Moreover, its cerebral blood flow is maintained rather than
increased during hypoxia
(Söderström et al.,
1999b
). In virtually all other vertebrates examined, from teleost
fishes and frogs to crocodiles, turtles and mammals, brain blood flow is
stimulated by hypoxia (Söderström et al.,
1999a
,b
;
Söderström-Lauritzen et al.,
2001
). Still, there appears to be a hypoxia-induced cerebral
vasodilation in the epaulette shark brain, since the shark displays a 50%
decrease in systemic blood pressure (accompanied by bradycardia) during
hypoxia (Söderström et al.,
1999b
). However, unlike most other vertebrates, adenosine does not
seem to be involved in the hypoxic cerebral vasodilation
(Söderström et al.,
1999b
).
Hypoxic-preconditioning primes metabolic and respiratory responses
Exposure to a non-lethal episode of hypoxia increases hypoxia tolerance in
both tolerant (Prosser et al.,
1957) and non-tolerant species
(Dirnagl et al., 2003
;
Samoilov et al., 2003
).
Interestingly, the way the epaulette shark is exposed to hypoxia on its reef
appears to be a natural parallel to the hypoxic pre-treatment regimen, termed
hypoxic-preconditioning in biomedical science. Initially during a period of
spring tides, the tides become lower and lower on subsequent nights.
Consequently, the epaulette shark will experience longer and longer periods of
hypoxia (Fig. 3).
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An experimental regimen of hypoxic-preconditioning prior to respirometry
shows that metabolic characteristics of the epaulette shark are significantly
altered. The rate of normoxic oxygen consumption is lowered by 30% and
there is a significant
20% drop in the shark's critical [O2],
bringing it close to the critical [O2] of the crucian carp and
goldfish (Routley et al.,
2002
). (The critical [O2] is the lowest oxygen
concentration where the routine rate of oxygen consumption can be maintained.)
Another study has shown that the deeper neural depression that the shark will
finally enter during anoxia (see below) is reached sooner if the shark has
been pre-exposed to anoxia (Renshaw et
al., 2002
). However, sharks retain the ability to enter metabolic
and ventilatory depression in response to anoxia even when they have been away
from the preconditioning effects of their natural environment for more than 6
months (G. M. C. Renshaw, unpublished).
Adenosine and metabolic depression in the epaulette shark
An elevated adenosine level acts as a trigger to disengage energy-expensive
cellular processes (Newby,
1984), regulate glycolytic rate, stimulate cerebral blood flow and
initiate metabolic depression in hypoxia- and anoxia-tolerant species
(Nilsson, 1991
;
Nilsson and Lutz, 1992
;
Perez-Pinzon et al., 1993
;
Boutilier, 2001
;
Lutz et al., 2003
).
Adenosine's net effect slows energy use while increasing anaerobic ATP
production to extend survival time.
While cerebral blood flow is not stimulated by adenosine during anoxia in
the epaulette shark (see above), it seems to play a role in the metabolic
depression of anoxic epaulette sharks. Exposing the epaulette shark to anoxia
resulted in a 3.5-fold increase in brain adenosine levels when compared with
normoxic controls (Renshaw et al.,
2002). Moreover, after
40 min in anoxia, the epaulette sharks
became unresponsive and lost their righting reflex while they still
successfully defended their brain ATP levels. Thus, at this stage they appear
to enter into a deeper phase of metabolic depression. Adenosine may be
particularly important for entering this second stage since sharks treated
with aminophylline, an adenosine receptor blocker, lost their righting reflex
much later, at a point when brain ATP levels had started to fall
(Renshaw et al., 2002
).
Interestingly, this first anoxic episode appeared to prime the sharks neural
depression, since a second anoxic episode 24 h later led to unresponsiveness
(with maintained brain [ATP]) within 20 min rather than 40
min(Renshaw et al., 2002
).
Glutamate and GABA in the epaulette shark brain
The ability to maintain brain glutamate homeostasis in response to low
oxygen levels distinguishes hypoxia- and anoxia-tolerant vertebrates from
intolerant species, which respond with a surge in extracellular glutamate
levels that ultimately culminates in neuronal death (see
Lutz et al., 2003 for a
review). In addition, hypoxia-tolerant species, as mentioned, show a
neuroprotective increase in GABA levels
(Nilsson, 1990
; Nilsson et
al., 1990
,
1991
;
Nilsson and Lutz, 1993
).
Histological staining for glutamate in epaulette shark brain
(Fig. 4A) indicates that
glutamate homeostasis is either maintained or significantly lowered in
descending axon tracts such as the median longitudinal fasciculus and the
fasciculus of Steida in the brainstem after exposure to hypoxia (5% of air
saturation; G. Wise and G. M. C. Renshaw, unpublished observations). In the
median longitudinal fasciculus, this was concomitant with a significant
increase in GABA, localised to small GABAergic neurons (J. M. Mulvey and G. M.
C. Renshaw, unpublished observations; Fig.
4B,C). These observations suggest that the epaulette shark may
utilise a changed balance between the GABA and glutamate transmitter systems
to induce metabolic depression in selected brain areas. Where glutamate levels
are maintained, these may be needed to re-establish neuronal activity once
oxygen is restored (Milton et al.,
2002
).
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GABA was significantly increased in motor nuclei and in some sensory nuclei
and maintained in sensory nuclei involved in vigilance (J. M. Mulvey and G. M.
C. Renshaw, unpublished observations). The pattern of increased GABA levels
closely followed the pattern of cytochrome oxidase staining indicative of
neuronal metabolism. Thus, reduced cytochrome oxidase activity was detected
histologically in the brainstem of epaulette sharks after hypoxic
pre-conditioning (Mulvey and Renshaw,
2000). The decrease was not uniform. Motor nuclei had
significantly more suppressed activities of cytochrome oxidase than sensory
nuclei, which appeared to maintain their metabolic activity. However, testing
the retinal light reflex has revealed that at least vision is temporarily
downregulated in response to hypoxia (K.-O. Stensløkken, G. E. Nilsson
and G. M. C. Renshaw, unpublished). The corresponding changes in cytochrome
oxidase activity and GABA immunoreactivity suggest the possibility that
increased inhibition is involved in the reduction in neuronal energy demands
to pre-empt a potential mismatch between energy supply and energy
consumption.
Modulation of GABAA receptors may also play a role in
hypoxia-induced preconditioning and metabolic depression. An upregulation of
GABAA receptors has been found in freshwater turtles
(Lutz and Kabler, 1995).
[3H]Ro 15-1788 binding was recently used to characterise
GABAA receptors in the brainstems of epaulette sharks exposed to
hypoxic-preconditioning or normoxia. There was an increase in maximal binding
capacity (Bmax) and dissociation constant
(KD), indicating receptor upregulation and increased
binding affinity in response to hypoxic-preconditioning (G. Wise and G. M. C.
Renshaw, unpublished observations). Hypoxic-preconditioning in the epaulette
shark resulted in significant increases in both the level of GABA and the
number of GABAA receptors. An increase in receptor number coupled
with an increase in receptor affinity should lead to a reduction in the
likelihood of neuronal depolarisation, by clamping or hyperpolarising the
membrane, and result in a significant energy saving.
Nitric oxide and possible neuroprotective changes in the cerebral vasculature
Endothelial cells sense changes in oxygen availability and can change their
phenotype to protect the endothelium from physiological stressors such as
hypoxia and anoxia (Pohlman and Harlan,
2000). One of the molecules produced by activated endothelial
cells is nitric oxide (NO), and there is a dramatic and highly significant
increase in the level of nitric oxide synthase (NOS) in the vasculature and
neurons in the epaulette shark in response to hypoxia
(Fig. 5; Renshaw and Dyson, 1999
).
While NO has been implicated in neuronal death, there is no evidence of
neuronal death in the epaulette shark brainstem after exposure to hypoxia
(Renshaw and Dyson, 1999
).
While the functional significance of NOS upregulation in the epaulette shark
in response to hypoxic challenge is unknown, it is evident that NO has diverse
intra- and extracellular roles that serve to reduce the extent of hypoxia
reperfusion injury in the mammalian heart
(Takano et al., 1998
;
Bolli, 2001
), restore ionic
homeostasis in the brain after cortical spreading depression
(Wang et al., 2003
) and
mediate ischemic tolerance after hypoxic preconditioning in a mammalian model
(Gidday et al., 1999
;
Willmot and Bath, 2003
).
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Conclusions |
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One immediate lesson to be learnt from the hypoxia-tolerant epaulette shark
is that adjustments such as an increased haematocrit, elevated blood [glucose]
or a rise in brain blood flow, which other vertebrates display in response to
hypoxia, are not always needed for anoxic survival. At least, the epaulette
shark can do without such responses. The physiological mechanisms conferring
protection in the epaulette shark must be multi-phase. On the respiratory
level, a changed pattern of gill blood flow and an elevated ventilatory
frequency will aid to facilitate oxygen uptake during moderate hypoxia. These
strategies are not sufficient to meet the challenge provided by progressive or
prolonged hypoxia. An altered metabolic status, probably stimulated by
increased levels of neuromodulatory metabolites such as adenosine, triggers
metabolic and ventilatory depression that is linked to the conservation of
brain energy charge in the epaulette shark
(Renshaw et al., 2002). In
addition, an alteration in the balance between excitatory and inhibitory
neurotransmitters occurs. The role of other modulatory factors has still to be
clarified, one being NOS, which displays profound changes in the epaulette
shark brain vasculature after hypoxia exposure.
With regard to both the crucian carp and the epaulette shark, it is clear that these animals offer an insight into convergent as well as divergent physiological strategies for anoxic survival. The tale of these two fishes is bound to continue.
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References |
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Bolli, R. (2001). Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. J. Mol. Cell. Cardiol. 33,1897 -1918.[CrossRef][Medline]
Boutilier, R. G. (2001). Mechanisms of cell survival in hypoxia and hypothermia. J. Exp. Biol. 204,3171 -3181.[Medline]
Burggren, W. W. (1982). "Air gulping" improves blood oxygen transport during aquatic hypoxia in the goldfish Carassius auratus. Physiol. Zool. 55,327 -334.
Dirnagl, U., Simon, R. P. and Hallenbeck, J. M. (2003). Ischemic tolerance and endogenous neuroprotection. Trends Neurosci. 26,248 -254.[CrossRef][Medline]
Duncan, J. A. and Storey, K. B. (1991). Subcellular enzyme binding and the regulation of glycolysis in anoxic turtle brain. Am. J. Physiol. Reg. Integ. Comp. Physiol. 262,R517 -R523.
Fernandes, M. N. and Rantin, F. T. (1989). Respirometry responses of Oreochromis niloticus (Pisces Cichilidae) to environmental hypoxia under different thermal conditions. J. Fish Biol. 35,509 -519.
Fraser, K. P. P., Houlihan, D. F., Lutz, P. L., Leone-Kabler, S., Manuel, L. and Brechin, J. G. (2001). Complete suppression of protein synthesis during anoxia with no post-anoxia protein synthesis debt in the red-eared slider turtle Trachemys scripta elegans.J. Exp. Biol. 204,4353 -4360.[Medline]
Gidday, J. M., Shah, A. R., Maceren, R. G., Wang, Q., Pelligrino, D. A., Holtzman, D. M. and Park, T. S. (1999). Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning. J. Cerebr. Blood Flow Metab. 19,331 -340.[Medline]
Hicks, J. M. T. and Farrell, A. P. (2000a). The
cardiovascular responses of the red eared slider (Trachemys scripta)
acclimated to either 22 or 5°C. I. Effects of anoxia exposure on in vivo
cardiac performance. J. Exp. Biol.
203,3765
-3774.
Hicks, J. M. T. and Farrell, A. P. (2000b). The
cardiovascular responses of the red eared slider (Trachemys scripta)
acclimated to either 22 or 5°C. II. Effects of anoxia on adrenergic and
cholinergic control. J. Exp. Biol.
203,3775
-3784.
Hylland, P. and Nilsson, G. E. (1999). Extracellular levels of amino acid neurotransmitters during anoxia and forced energy deficiency in crucian carp brain. Brain Res. 823, 49-58.[CrossRef][Medline]
Hylland, P., Nilsson, G. E. and Lutz, P. L. (1994). Time course of anoxia induced increase in cerebral blood flow rate in turtles: evidence for a role of adenosine. J. Cereb. Blood Flow Metab. 14,877 -881.[Medline]
Hyvärinen, H., Holopainen, I. J. and Piironen, J. (1985). Anaerobic wintering of crucian carp (Carassius carassius L.) I. Annual dymanics of glycogen reserves in nature. Comp. Biochem. Physiol. A 82,797 -803.[CrossRef]
Jackson, D. C. (1968). Metabolic depression and
oxygen depletion in the diving turtle. J. Appl.
Physiol. 24,503
-509.
Johansson, D. and Nilsson, G. E. (1995). Roles of energy status, KATP channels and channel arrest in fish brain K+ gradient dissipation during anoxia. J. Exp. Biol. 198,2575 -2580.[Medline]
Johansson, D., Nilsson, G. E. and Törnblom, E.
(1995). Effects of anoxia on energy metabolism in crucian carp
brain slices studied with microcalorimetry. J. Exp.
Biol. 198,853
-859.
Johansson, D., Nilsson, G. E. and Døving, K. B. (1997). Anoxic depression of light-evoked potentials in retina and optic tectum of crucian carp. Neurosci. Lett. 237, 73-76.[CrossRef][Medline]
Lushchak, V., Lushchak, L. P., Mota, A. A. and Hermes-Lima,
M. (2001). Oxidative stress and antioxidant defenses in
goldfish Carassius auratus during anoxia and reoxygenation.
Am. J. Physiol. Integ. Reg. Comp. Physiol.
280,R100
-R107.
Lutz, P. L. and Kabler, S. A. (1995).
Upregulation of GABAA receptor during anoxia in the turtle brain.
Am. J. Physiol. Integ. Reg. Comp. Physiol.
268,R1332
-R1335.
Lutz, P. L. and Nilsson, G. E. (1997).
Contrasting strategies for anoxic brain survival glycolysis up or
down. J. Exp. Biol. 200,411
-419.
Lutz, P. L., Nilsson, G. E. and Prentice, H. M. (2003). The Brain Without Oxygen: Causes of Failure Physiological and Molecular Mechanisms for survival. Third edition. Dordrecht: Kluwer Academic Publishers.
Milton, S. L., Thompson, J. W. and Lutz, P. L.
(2002). Mechanisms for maintaining extracellular glutamate levels
in the anoxic turtle striatum. Am. J. Physiol. Regul. Integ. Comp.
Physiol. 282,R1317
-R1323.
Mulvey, J. M. and Renshaw, G. M. C. (2000). Neuronal oxidative hypometabolism in the brainstem of the epaulette shark (Hemiscylium ocellatum) in response to hypoxic pre-conditioning. Neurosci. Lett. 290,1 -4.[CrossRef][Medline]
Muuse, B., Marcon, J., van den Thillart, G. and AlmeidaVal, V. (1998). Hypoxia tolerance in Amazon fish respirometry and energy metabolism of the cichlid Astronotus ocellatus. Comp Biochem. Physiol. A 120,151 -156.
Newby, A. C. (1984). Adenosine and the concept of "retaliatory metabolites". Trends Biochem. Sci. 9,42 -44.[CrossRef]
Nilsson, G. E. (1990). Long-term anoxia in crucian carp: changes in the levels of amino acid and monoamine neurotransmitters in the brain, catecholamines in chromaffin tissue, and liver glycogen. J. Exp. Biol. 150,295 -320.[Abstract]
Nilsson, G. E. (1991). The adenosine receptor
blocker aminophylline increases anoxic ethanol excretion in crucian carp.
Am. J. Physiol. Reg. Integ. Comp. Physiol.
261,R1057
-R1060.
Nilsson, G. E. (2001). Surviving anoxia with the brain turned on. News Physiol. Sci. 16,218 -221.
Nilsson, G. E. and Lutz, P. L. (1991). Release
of inhibitory neurotransmitters in response to anoxia in turtle brain,
Am. J. Physiol. Reg. Integ. Comp. Physiol.
261,R32
-R37.
Nilsson, G. E. and Lutz, P. L. (1992). Adenosine release in the anoxic turtle brain: a possible mechanism for anoxic survival. J. Exp. Biol. 162,345 -351.
Nilsson, G. E. and Lutz, P. L. (1993). Role of GABA in hypoxia tolerance, metabolic depression and hibernation possible links to neurotransmitter evolution. Comp. Biochem. Physiol. C 105,329 -336.[Medline]
Nilsson, G. E., Alfaro, A. A. and Lutz, P. L.
(1990). Changes in turtle brain neurotransmitters and related
substances during anoxia. Am. J. Physiol. Integ. Reg. Comp.
Physiol. 259,R376
-R384.
Nilsson, G. E., Lutz, P. L. and Jackson, T. L. (1991). Neurotransmitters and anoxic survival of the brain: a comparison between anoxia-tolerant and anoxia-intolerant vertebrates. Physiol. Zool. 64,638 -652.
Nilsson, G. E., Rosén, P. and Johansson, D.
(1993). Anoxic depression of spontaneous locomotor activity in
crucian carp quantified by a computerized imaging technique. J.
Exp. Biol. 180,153
-162.
Nilsson, G. E., Hylland, P. and Löfman, C. O.
(1994). Anoxia and adenosine induce increased cerebral blood flow
in crucian carp. Am. J. Physiol. Integ. Reg. Comp.
Physiol. 267,R590
-R595.
Nilsson, G. E. and Östlund-Nilsson, S. (2004). Hypoxia in paradise: widespread hypoxia tolerance in coral reef fishes. Proc. Roy. Soc. B 271,S30 -S33.[Medline]
Perez-Pinzon, M. A., Lutz, P. L., Sick, T. J. and Rosenthal, M. (1993). Adenosine, a "retaliatory" metabolite, promotes anoxia tolerance in turtle brain. J. Cereb. Blood Flow Metab. 13,728 -732.[Medline]
Pohlman, T. H. and Harlan, J. M. (2000). Adaptive responses of the endothelium to stress. J. Surg. Res. 89,85 -119.[CrossRef][Medline]
Poli, A., Beraudi, A., Villani, L., Storto, M., Battaglia, G.,
Gerevini, V. D. G., Capuccio, I., Caricasole, A., D'Onofrio, M. and Nicoletti,
F. (2003). Group II metabotropic glutamate receptors regulate
the vulnerability to hypoxic brain damage. J.
Neurosci. 23,6023
-6029.
Prosser, C. L., Barr, L. M., Pinc, R. D. and Lauer, C. Y. (1957). Acclimation of goldfish to low concentrations of oxygen. Physiol. Zool. 30,137 -141.
Renshaw, G. M. C. and Dyson, S. E. (1999). Increased nitric oxide synthase in the vasculature of the epaulette shark brain following hypoxia. Neuroreport 10,1707 -1712.[Medline]
Renshaw, G. M. C., Kerrisk, C. B. and Nilsson, G. E. (2002). The role of adenosine in the anoxic survival of the epaulette shark, Hemiscyllium ocellatum. Comp. Biochem. Physiol. B 131,133 -141.[CrossRef][Medline]
Rosati, A. M., Traversa, U., Lucchi, R. and Poli, A. (1995). Biochemical and pharmacological evidence for the presence of A1 but not A2a adenosine receptors in the brain of the low vertebrate teleost Carassius auratus (goldfish). Neurochem. Int. 26,411 -423.[CrossRef][Medline]
Routley, M. H., Nilsson, G. E. and Renshaw, G. M. C. (2002). Exposure to hypoxia primes the respiratory and metabolic responses of the epaulette shark to progressive hypoxia. Comp. Biochem. Physiol. A 131,313 -321.
Samoilov, M. O., Lazarevich, E. V., Semenov, D. G. and Mokrushin, A. (2003). The adaptive preconditioning of brain neurons. Neurosci. Behav. Physiol. 33, 1-11.[CrossRef][Medline]
Smith, R. W., Houlihan, D. F., Nilsson, G. E. and Brechin, J.
G. (1996). Tissue specific changes in protein synthesis rates
in vivo during anoxia in crucian carp. Am. J. Physiol. Integ. Reg.
Comp. Physiol. 271,R897
-R904.
Söderström, V., Nilsson, G. E., Renshaw, G. M. C. and Franklin, C. E. (1999a). Hypoxia stimulates cerebral blood flow in the estuarine crocodile (Crocodylus porosus). Neurosci. Lett. 267,1 -4.[CrossRef][Medline]
Söderström, V., Renshaw, G. M. C. and Nilsson, G.
E. (1999b). Brain blood flow and blood pressure during
hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia
tolerant elasmobranch. J. Exp. Biol.
202,829
-835.
Söderström-Lauritzen, V., Nilsson, G. E. and Lutz, P. L. (2001). Effect of anoxia and adenosine on cerebral blood flow in the leopard frog (Rana pipens). Neurosci. Lett. 311,85 -88.[CrossRef][Medline]
Sollid, J., De Angelis, P., Gundersen, K. and Nilsson, G. E.
(2003). Hypoxia induces adaptive and reversible gross
morphological changes in crucian carp gills. J. Exp.
Biol. 206,3667
-3673.
Stecyk, J. A. W., Overgaard, J., Farrell, A. P. and Wang, T.
(2004). Alfa-adrenergic regulation of systemic peripheral
resistance and blood flow distribution in the turtle Trachemys
scripta during anoxic submergence at 5°C and 21°C. J.
Exp. Biol. 207,269
-283.
Suzue, T., Wu, G.-B. and Furukawa, T. (1987).
High susceptibility to hypoxia of afferent synaptic transmission in the
goldfish sacculus. J. Neurophysiol.
58,1066
-1079.
Takano, H., Tang, X. L., Qiu, Y., Guo, Y., French, B. A. and
Bolly, R. (1998). Nitric oxide donors induce late
preconditioning against myocardial stunning and infarction in conscious
rabbits via an antioxidant-sensitive mechanism. Circ.
Res. 83,73
-84.
Ultsch, G. R. and Jackson, D. C. (1982). Long-term submergence at 3°C of the turtle, Chrysemys picta belli, in normoxic and severely hypoxic water. I. Survival, gas exchange and acid-base status. J. Exp. Biol. 96, 11-28.
Ultsch, G. R., Jackson, D. C. and Moalli, R. (1981). Metabolic oxygen conformity among lower vertebrates: the toadfish revisited. J. Comp. Physiol. 142,439 -443.
Val, A. L., Silva, M. N. P. and Almeida-Val, V. M. F. (1998). Hypoxia adaptation in fish of the Amazon: a never-ending task. S. Afr. J. Zool. 33,107 -114.
Van Ginneken, V., Nieveen, M., Van Eersel, R., Van den Thillart, G. and Addink, A. (1996). Neurotransmitter levels and energy status in brain of fish species with and without the survival strategy of metabolic depression. Comp. Biochem. Physiol. A 114,189 -196.[CrossRef]
Van Waarde, A. (1991). Alcoholic fermentation in multicellular organisms. Physiol. Zool. 64,895 -920.
Van Waversveld, J., Addink, A. D. F. and Van den Thillart, G. (1989). Simultaneous direct and indirect calorimetry on normoxic and anoxic goldfish. J. Exp. Biol 142,325 -335.
Wang, M., Obrenovitch, T. P. and Urenjak, J. (2003). Effects of the nitric oxide donor, DEA/NO on cortical spreading depression. Neuropharmacology 44,949 -957.[CrossRef][Medline]
Willmot, M. R. and Bath, P. M. (2003). The potential of nitric oxide therapeutics in stroke. Expert Opin. Inv. Drug. 12,455 -470.[CrossRef]
Wise, G., Mulvey, J. M. and Renshaw, G. M. C. (1998). Hypoxia tolerance in the epaulette shark (Hemiscyllium ocellatum). J. Exp. Zool. 281, 1-5.[CrossRef]
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