The effect of audiogenic seizures on regional CNS energy reserves, glycolysis and citric acid cycle flux

Selected energy reserves, glycolytic intermediates and citric acid cycle intermediates were measured in the cerebral cortex, thalamus, brain stem, cerebellum and spinal cord of susceptible mice during audiogenic seizures. Changes in energy reserves (ATP, phosphocreatine and glucose) differed strikingly in extent and temporal pattern from region to region. The audiogenic seizure produced a transient, large decrease in thalamic energy reserves during the early, pretonic phase of the seizure. Less extensive decreases were observed in brain stem and spinal cord; but in these latter regions the changes persisted throughout the pretonic and tonic phases of the seizures. In cerebellum there was a biphasic decrease in energy reserves; a small decrease was observed immediately after the sound stimulus and a second much greater decrease was observed during the tonic phase of the seizure. No change in energy reserves was observed in cerebral cortex. Changes in glycolytic intermediates (glucose 6-phosphate, fructose diphosphate, pyruvate and lactate) also varied from region to region in response to the decreases in energy reserves. In contrast, changes in the two citric acid cycle intermediates, α-oxoglutarate and malate, were essentially the same in all regions studied. α-Oxoglutarate decreased during the tonic phase of the seizure and rose during recovery. Malate remained at control levels throughout the seizure and then slowly increased. These findings are interpreted as indicating regional variations in nueronal activity during audiogenic seizures. During the period when clinical seizure activity is apparent neuronal activity increases in the subcortical regions. This is reflected by an increase in energy utilization and an increase in glycolytic flux in these areas. However, a concomitant increase in citric acid cycle flux does not seem to occur during this period. Citric acid cycle flux does appear to increase after the seizure is over.     

The effect of energy reserves and food availability on optimal immune defence

In order to avoid both starvation and disease, animals must allocate resources between energy reserves and immune defence. We investigate the optimal allocation. We find that animals with low reserves choose to allocate less to defence than animals with higher reserves because when reserves are low it is more important to increase reserves to reduce the risk of starvation in the future. In general, investment in immune defence increases monotonically with energy reserves. An exception is when the animal can reduce its probability of death from disease by reducing its foraging rate. In this case, allocation to immune defence can peak at intermediate reserves. When food changes over time, the optimal response depends on the frequency of changes. If the environment is relatively stable, animals forage most intensively when the food is scarce and invest more in immune defence when the food is abundant than when it is scarce. If the environment changes quickly, animals forage at low intensity when the food is scarce, but at high intensity when the food is abundant. As the rate of environmental change increases, immune defence becomes less dependent on food availability. We show that the strength of selection on reserve-dependent immune defence depends on how foraging intensity and immune defence determine the probability of death from disease.     

The effect of thermoregulatory substitution on optimal energy reserves of small birds in winter

Previous models have predicted the body mass of small birds in winter on the basis of a trade-off between starvation and predation. Many of these models have assumed that energy expenditure while active increases with body mass. The implications of the fact that the metabolic cost of activity can substitute for internal heat production and help keep the bird warm have not been investigated. In this paper we show that if thermoregulatory substitution occurs then there is a critical level of energy reserves above which an active bird is thermoneutral. This critical level increases as temperature decreases. Below this level, substitution of energy results in higher optimal levels of reserves than would be predicted in the absence of substitution. Our model thus predicts that at low temperatures body mass will be higher when thermoregulatory substitution occurs.     

The effect of energy reserves on social foraging: hungry sparrows scrounge more

Animals often use alternative strategies when they compete for resources, but it is unclear in most cases what factors determine the actual tactic followed by individuals. Although recent models suggest that the internal state of animals may be particularly important in tactic choice, the effects of state variables on the use of alternative behavioural forms have rarely been demonstrated. In this study, using experimental wind exposure to increase overnight energy expenditure, we show that flock-feeding house sparrows (Passer domesticus) with lowered energy reserves increase their use of scrounging (exploiting others' food findings) during their first feed of the day. This result is in accordance with the prediction of a state-dependent model of use of social foraging tactics. We also show that scrounging provides less variable feeding rates and patch finding times than the alternative tactic. These latter results support the theoretical assumption that scrounging is a risk-averse tactic, i.e. it reduces the risk of immediate starvation. As the level of energy reserves predicts the use of social foraging tactics, we propose that selection should favour individuals that monitor the internal state of flock mates and use this information to adjust their own tactic choice.     

A theoretical investigation of the effect of predators on foraging behaviour and energy reserves

Data show that when small birds are exposed to a model of a predator, their body mass may either increase or decrease. Although attempts have been made to explain the data using previous models, these models are based on a constant level of predation and hence are not appropriate for making predictions about the response of a bird to the sight of a predator. We have developed a novel model that includes encounters between a bird and potential predators. We show that, depending on the biology of the predator, optimal body mass may either increase or decrease. The model also makes predictions about the foraging behaviour of the bird after it has seen a predator.     

The effect of overwintering temperature on the body energy reserves and phenoloxidase activity of bumblebee Bombus lucorum queens

Warming winters and changes in species composition related to the estimated global warming may cause a threat to bumblebees adapted to cold winters. During the overwintering period, their intermediary and respiratory metabolism decreases but metabolism remains responsive to temperature. The effect of temperature on diapause survival, phenoloxidase (PO) activity, and energy expenditure of the white-tailed bumblebee (Bombus lucorum) after a 4-month diapause were studied by manipulating the diapause temperature. Two overwintering temperatures were used, cold (1.8 °C) and warm (9 °C). Body fat content was used as an estimate of the remaining energy resources and PO activity as an immune function parameter of overwintering bumblebee queens. The baseline levels of PO activity were used to measure the differences in B. lucorum queen responses after overwintering in either temperature. We found a 0.4 g pre-diapause threshold weight of survival in B. lucorum. Large queens had more fat left and a higher PO activity compared to small ones after overwintering in warm conditions, but in the cold there was no effect of size on the remaining fat in the fat body of queens or their PO activity. The observed difference in energy usage appears to relate to normal size-dependent metabolism and variation in energy allocation between basic metabolism and immune functions.     

The effect of Metarhizium anisopliae var acridum on haemolymph energy reserves and flight capability in the desert locust, Schistocerca gregaria

Adult desert locusts, Schistocerca gregaria , 3 days after inoculation with the entomopathogenic fungus Metarhizium anisopliae var acridum , had significantly less carbohydrate and lipid in the haemolymph than controls. This was not due to reduced food intake as 3 days of complete starvation had no effect on haemolymph titres of energy reserves in controls. Furthermore injection of an extract of the corpora cardiaca (the source of adipokinetic hormone, AKH) caused a large significant increase in haemolymph lipid in mycosed locusts, indicating the availability of significant quantities of lipid in the fat body, the target for AKH. Haemolymph carbohydrate declined significantly during tethered flight of control locusts but not in mycosed individuals. An injected supplement of trehalose significantly boosted flight performance of mycosed insects but not controls. The results are discussed in the light of the hypothesis that the poor flight capability of mycosed locusts is due in part to a fungus-induced reduction in mobile energy reserves.     

Use of energy reserves in fighting hermit crabs

When animals engage in fights they face a series of decisions, which are based on the value of the contested resource and either their relative or their absolute fighting ability. Certain correlates of fighting ability or 'resource holding potential' such as body size are fixed but physiological correlates are expected to vary during the encounter. We examine the role of energy reserves in determining fight outcomes and parameters during 'shell fighting' in hermit crabs. During these fights, the two contestants perform very different roles of attacker and defender. We show that the balance of the total energy pool, in the form of glucose and glycogen, determines the ability of defenders to resist eviction from their shells. Low glucose in evicted defenders is not caused by depletion of energy reserves, rather mobilization of glycogen appears to be the result of a strategic decision about whether to resist effectively, based on the perceived fighting ability of the attacker. Attackers, however, always initiate the fight so such a decision for this role appears unlikely. In addition to influencing decisions and ability during fights, physiological correlates of fighting ability can in turn be influenced by strategic decisions.     

Effects of antiepileptic drugs on brain energy reserves during convulsions

Cerebral cortical ATP, P-creatine, glucose, and lactate were measured 6 sec after 1 sec of 150/sec rectangular pulses, at 0,20 v, 40 v, 60 v, 80 v, or 100 v, applied to the heads of intact mice which had been given either no drug, phenobarbitone (25 mg/kg), trimethadione (600 mg/kg), or diphenylhydantoin (40 mg/kg), intraperitoneally. In general, regardless of stimulus strength or drug used, animals which exhibited maximal (tonic-clonic) convulsions showed similar striking decreases in brain P-creatine, decreases in ATP and glucose, and increases in lactate. On the other hand, in animals which exhibited less than maximal clinical response, there was little or no change in these metabolites. An exception was the case of diphenylhydantoin. Tonic-clonic seizures did not occur after diphenylhydantoin administration, even with 100 v stimuli, but substrate changes at this voltage were, nevertheless, similar to those observed in brains of other mice undergoing maximal convulsions.     

Effect of beta-adrenoceptor antagonists and some related drugs on maximal electroshock seizures in mice

(+/-) Propranolol (1-50 mg/kg), (+) propranolol (50 mg/kg) and pindolol (10-50 mg/kg) exhibited significant protective effects against MES (maximum electroshock seizures), whereas, timolol (1 mg/kg), the propranolol analog, UM-272 (1 and 10 mg/kg), and the beta-agonist, terbutaline (1 and 10 mg/kg) were ineffective. Cholinergic agents, physostigmine (0.01-1.0 mg/kg), and atropine (1 and 10 mg/kg), the serotonin antagonist, cyproheptadine (0.05 mg/kg), and the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg), were also without effect on the MES extensor phase. Further, pretreatment of mice with terbutaline, atropine, cyproheptadine or indomethacin did not influence the anti-MES effect of propranolol to any significant extent. The results indicate that the observed anticonvulsant effects of beta-adrenoceptor antagonists are unrelated to noradrenergic or other central neurotransmitter systems and that a non-specific mechanism, probably a membrane stabilizing effect is involved.     

Effects of duration of convulsions on energy reserves of the brain

Abstract— Rapid administration (0·4 ml in 1 sec) of the convulsant inhalant, flurothyl (hexafluorodiethyl ether, indoklon), to mice induced within 10 sec clonic-tonic seizures that were accompanied by marked decrease of P-creatine, decrease of ATP and glucose, and increase of lactate in the cerebral cortex. In contrast, mice to which flurothyl had been administered slowly (0·05 ml every 30 sec for 10 min) exhibited myoclonic jerks after about 3 min, merging into irregular clonus at about 5 min, and intermittent clonus thereafter until onset of tonic hind limb extension at about 10 min. In these mice, P-creatine in cerebral cortex decreased gradually for 6 min and then remained through 10 min at levels nearly as low as those reached 10 sec after rapidly administered flurothyl. Lactate in cerebral cortex increased much more during the 10 min of slow administration of flurothyl than in 10 sec of rapid administration, the greatest increase occurring at 4–6 min, as myoclonic jerks merged into irregular clonus. Glucose and ATP in cerebral cortex fluctuated somewhat but did not decrease greatly when flurothyl was administered slowly.