Heat shock response and ageing: mechanisms and applications

Ageing is associated with a decrease in the ability of cells to cope with environmental challenges. This is due partly to the attenuation of a primordial stress response, the so-called heat shock (HS) response, which induces the expression of heat shock proteins (HSPs), composed of chaperones and proteases. The attenuation of the HS response during ageing may be responsible for the accumulation of damaged proteins as well as abnormal regulation of cell death. Maintenance of the HS response by repeated mild heat stress causes anti-ageing hormetic effects on cells and organisms. Here, we describe the molecular mechanism and the state of the HS response as well as the role of specific HSPs during ageing, and discuss the possibility of hormetic modulation of ageing and longevity by repeated mild stress.     

Temperature‐induced developmental plasticity in Plodia interpunctella: Reproductive behaviour and sperm length

In both plants and animals, male gametogenesis is particularly sensitive to heat stress, to the extent that a single hot or cold day can compromise crop productivity or population persistence. In animals, heat stress during development can impact a male's ability to secure copulations and/or his post‐copulatory fertility. Despite such observations, relatively few studies have examined the consequences of developmental temperature on the reproductive behaviour and physiology of individuals. Here, we report for the first time the effects of developmental temperature on the phenotypic expression of both apyrene and eupyrene sperm and the copulatory behaviour of the Indian meal moth, Plodia interpunctella. We show that the length of both apyrene and eupyrene sperm decreases with increasing developmental temperature and that males are less likely to engage in copulation when reared at the highest and lowest temperatures. Where copulation occurred, the duration of copula decreased as male developmental temperature increased. We argue that identification of the mechanisms and consequences of reproductive failure in animals facing heat stress will help understand how wild and domesticated populations will respond to global climate change. We also contend that such studies will help elucidate long‐standing evolutionary questions around the maintenance of genetic variation in traits highly relevant to fitness and the role of phenotypic plasticity in driving the evolution of novel traits.     

Heat shock‐induced thermoprotection of action potentials in the locust flight system

There is increasing evidence that heat shock (HS) has long‐term effects on electrophysiological properties of neurons and synapses. Prior HS protects neural circuitry from a subsequent heat stress but little is known about the mechanisms that mediate this plasticity and induce thermotolerance. Exposure of Locusta migratoria to HS conditions of 45°C for 3 h results in thermotolerance to hitherto lethal temperatures. Locust flight motor patterns were recorded during tethered flight at room temperature, before and after HS. In addition, intracellular action potentials (APs) were recorded from control and HS motoneurons in a semi‐intact preparation during a heat stress. HS did not alter the timing of representative depressor or elevator muscle activity, nor did it affect the ability of the locust to generate a steering motor pattern in response to a stimulus. However, HS did increase the duration of APs recorded from neuropil segments of depressor motoneurons. Increases in AP duration were associated with protection of AP generation against failure at subsequent elevated temperatures. Failure of AP generation at high temperatures was preceded by a concomitant burst of APs and depolarization of the membrane. The protective effects of HS were mimicked by pharmacological blockade of I with tetraethylammonium (TEA). Taken together, these findings are consistent with a hypothesis that HS protects neuronal survival and function via K⁺ channel modulation. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 188–199, 2001     

Metabolic and hormonal acclimation to heat stress in domesticated ruminants

Environmentally induced periods of heat stress decrease productivity with devastating economic consequences to global animal agriculture. Heat stress can be defined as a physiological condition when the core body temperature of a given species exceeds its range specified for normal activity, which results from a total heat load (internal production and environment) exceeding the capacity for heat dissipation and this prompts physiological and behavioral responses to reduce the strain. The ability of ruminants to regulate body temperature is species- and breed-dependent. Dairy breeds are typically more sensitive to heat stress than meat breeds, and higher-producing animals are more susceptible to heat stress because they generate more metabolic heat. During heat stress, ruminants, like other homeothermic animals, increase avenues of heat loss and reduce heat production in an attempt to maintain euthermia. The immediate responses to heat load are increased respiration rates, decreased feed intake and increased water intake. Acclimatization is a process by which animals adapt to environmental conditions and engage behavioral, hormonal and metabolic changes that are characteristics of either acclimatory homeostasis or homeorhetic mechanisms used by the animals to survive in a new 'physiological state'. For example, alterations in the hormonal profile are mainly characterized by a decline and increase in anabolic and catabolic hormones, respectively. The response to heat load and the heat-induced change in homeorhetic modifiers alters post-absorptive energy, lipid and protein metabolism, impairs liver function, causes oxidative stress, jeopardizes the immune response and decreases reproductive performance. These physiological modifications alter nutrient partitioning and may prevent heat-stressed lactating cows from recruiting glucose-sparing mechanisms (despite the reduced nutrient intake). This might explain, in large part, why decreased feed intake only accounts for a minor portion of the reduced milk yield from environmentally induced hyperthermic cows. How these metabolic changes are initiated and regulated is not known. It also remains unclear how these changes differ between short-term v. long-term heat acclimation to impact animal productivity and well-being. A better understanding of the adaptations enlisted by ruminants during heat stress is necessary to enhance the likelihood of developing strategies to simultaneously improve heat tolerance and increase productivity.     

Local adaptation of reproductive performance during thermal stress

Considerable evidence exists for local adaptation of critical thermal limits in ectotherms following adult temperature stress, but fewer studies have tested for local adaptation of sublethal heat stress effects across life‐history stages. In organisms with complex life cycles, such as holometabolous insects, heat stress during juvenile stages may severely impact gametogenesis, having downstream consequences on reproductive performance that may be mediated by local adaptation, although this is rarely studied. Here, we tested how exposure to either benign or heat stress temperature during juvenile and adult stages, either independently or combined, influences egg‐to‐adult viability, adult sperm motility and fertility in high‐ and low‐latitude populations of Drosophila subobscura. We found both population‐ and temperature‐specific effects on survival and sperm motility; juvenile heat stress decreased survival and subsequent sperm motility and each trait was lower in the northern population. We found an interaction between population and temperature on fertility following application of juvenile heat stress; although fertility was negatively impacted in both populations, the southern population was less affected. When the adult stage was also subject to heat stress, the southern population exhibited positive carry‐over effects whereas the northern population's fertility remained low. Thus, the northern population is more susceptible to sublethal reproductive consequences following exposure to juvenile heat stress. This may be common in other organisms with complex life cycles and current models predicting population responses to climate change, which do not take into account the impact of juvenile heat stress on reproductive performance, may be too conservative.     

Heat shock-induced thermoprotection of action potentials in the locust flight system.

There is increasing evidence that heat shock (HS) has long-term effects on electrophysiological properties of neurons and synapses. Prior HS protects neural circuitry from a subsequent heat stress but little is known about the mechanisms that mediate this plasticity and induce thermotolerance. Exposure of Locusta migratoria to HS conditions of 45 degrees C for 3 h results in thermotolerance to hitherto lethal temperatures. Locust flight motor patterns were recorded during tethered flight at room temperature, before and after HS. In addition, intracellular action potentials (APs) were recorded from control and HS motoneurons in a semi-intact preparation during a heat stress. HS did not alter the timing of representative depressor or elevator muscle activity, nor did it affect the ability of the locust to generate a steering motor pattern in response to a stimulus. However, HS did increase the duration of APs recorded from neuropil segments of depressor motoneurons. Increases in AP duration were associated with protection of AP generation against failure at subsequent elevated temperatures. Failure of AP generation at high temperatures was preceded by a concomitant burst of APs and depolarization of the membrane. The protective effects of HS were mimicked by pharmacological blockade of I(K+) with tetraethylammonium (TEA). Taken together, these findings are consistent with a hypothesis that HS protects neuronal survival and function via K+ channel modulation.     

Conserved and novel heat stress‐responsive microRNAs were identified by deep sequencing in Saccharina japonica (Laminariales,Phaeophyta)

As a temperate‐cold species, Saccharina japonica often suffers heat stress when it is transplanted to temperate and subtropical zones. Study the heat stress response and resistance mechanism of Saccharina is of great significance for understanding the acclimation to heat stress under domestication as well as for breeding new cultivars with heat stress resistance. In this study, we identified a set of heat stress‐responsive miRNAs and analysed their regulation during the heat stress response. CO (control) and heat stress (HS) sRNA libraries were constructed and sequenced. Forty‐nine known miRNAs and 75 novel miRNAs were identified, of which seven known and 25 novel miRNAs were expressed differentially under heat stress. Quantitative PCR of six selected miRNAs confirmed that these loci were responsive to heat stress. Thirty‐nine and 712 genes were predicted to be targeted by the seven known miRNAs and 25 novel miRNAs, respectively. Gene function and pathway analyses showed that these genes probably play important roles in S. japonica heat stress tolerance. The miRNAs identified represent the first set of heat‐responsive miRNAs identified from S. japonica, and their identification can help elucidate the heat stress response and resistance mechanisms in S. japonica.     

Short term post-partum heat stress in dairy cows

Since many dairy cows calve during late summer, the objective was to determine if heat stress immediately post-partum would (1) alter metabolism, thus, increasing susceptibility to metabolic disorders, (2) affect lactation and/or (3) affect reproduction. Forty four cows, calving during late summer, were paired with one member of each pair stressed (HS) for the first 10 post-partum days in a hot barn. Controls (CC) were kept in a cooled section of the barn. Plasma drawn weekly for 7 weeks was analyzed in an autoanalyzer for calcium, inor. phosphorus, protein, glucose and cholesterol and by radioimmunoassay for cortisol and progesterone. Ovaries and uteri were palpated weekly. Rectal temperatures were significant higher for HS during the first 10 post-partum days. No significant effects on plasma constituents were observed during the 10-day treatment period. For the 7-week period, glucose and cholesterol were lower in HS, as were cyclic peaks of progesterone and cortisol. Both calcium and inorganic phosphorus remained clinically low for the 7 weeks, but no treatment effects were seen. Uteri of HS involuted more rapidly than the CC. Treatment did not affect reproductive efficiency. Lactation milk yields did not differ, but milk fat percent was lower in HS. Heat stress immediately post-partum altered lipid metabolism, but the animal's compensatory mechanisms prevented reduction in milk production or reproductive efficiency.Journal Paper No. 4227 Mississippi Agricultural and Forestry Experiment Station.Presented at the Eighth International Congress of Biometeorology, 9–14 September 1979, Shefayim, Israel.     

Heat stress-induced apoptosis in porcine in vitro fertilized and parthenogenetic preimplantation-stage embryos

Decades worth of research have consistently shown the adverse effects of elevated temperatures on reproductive parameters of livestock species. The objective of this study was to evaluate the developmental and apoptotic responses of porcine in vitro fertilized (IVF) and parthenogenetically activated (PA) embryos heat stressed at the late 1-cell stage. Embryos were heat stressed (HS) at 42 degrees C for 9 hr starting 22 hr after insemination or artificial activation stimulus. Non heat-stressed (NHS) control embryos were maintained at 39 degrees C for the duration of the experiments. TUNEL staining on Day 5 of development demonstrated that heat stress elicited a significant apoptotic response in IVF embryos (45.6% of HS embryos and 26.7% of NHS embryos were apoptotic; P<0.05), but not in PA embryos (51.1% and 39.9% for HS and NHS embryos, respectively; P>0.1). And, while IVF embryos were highly susceptible to heat-induced developmental perturbations (20.6% and 8.8% development to blastocyst for NHS and HS embryos, respectively; P<0.05), elevated temperatures did not affect blastocyst rates in PA embryos (22.2% for NHS PA embryos and 21.2% for HS PA embryos; P>0.1). These findings indicate that, as in other systems studied, IVF pig embryos are directly affected adversely by heat stress conditions. Parthenogenetic embryos, though, appear to be surprisingly tolerant of the elevated temperatures. The differences between IVF and PA embryos in their response to heat stress warrants further investigation.     

A regulatory role of autophagy for resetting the memory of heat stress in plants

As sessile life forms, plants are repeatedly confronted with adverse environmental conditions, which can impair development, growth, and reproduction. During evolution, plants have established mechanisms to orchestrate the delicate balance between growth and stress tolerance, to reset cellular biochemistry once stress vanishes, or to keep a molecular memory, which enables survival of a harsher stress that may arise later. Although there are several examples of memory in diverse plants species, the molecular machinery underlying the formation, duration, and resetting of stress memories is largely unknown so far. We report here that autophagy, a central self‐degradative process, assists in resetting cellular memory of heat stress (HS) in Arabidopsis thaliana. Autophagy is induced by thermopriming (moderate HS) and, intriguingly, remains high long after stress termination. We demonstrate that autophagy mediates the specific degradation of heat shock proteins at later stages of the thermorecovery phase leading to the accumulation of protein aggregates after the second HS and a compromised heat tolerance. Autophagy mutants retain heat shock proteins longer than wild type and concomitantly display improved thermomemory. Our findings reveal a novel regulatory mechanism for HS memory in plants.     

Yield response of field‐grown soybean exposed to heat waves under current and elevated [CO2]

Elevated atmospheric CO₂ concentration ([CO₂]) generally enhances C₃ plant productivity, whereas acute heat stress, which occurs during heat waves, generally elicits the opposite response. However, little is known about the interaction of these two variables, especially during key reproductive phases in important temperate food crops, such as soybean (Glycine max). Here, we grew soybean under elevated [CO₂] and imposed high‐ (+9°C) and low‐ (+5°C) intensity heat waves during key temperature‐sensitive reproductive stages (R1, flowering; R5, pod‐filling) to determine how elevated [CO₂] will interact with heat waves to influence soybean yield. High‐intensity heat waves, which resulted in canopy temperatures that exceeded optimal growth temperatures for soybean, reduced yield compared to ambient conditions even under elevated [CO₂]. This was largely due to heat stress on reproductive processes, especially during R5. Low‐intensity heat waves did not affect yields when applied during R1 but increased yields when applied during R5 likely due to relatively lower canopy temperatures and higher soil moisture, which uncoupled the negative effects of heating on cellular‐ and leaf‐level processes from plant‐level carbon assimilation. Modeling soybean yields based on carbon assimilation alone underestimated yield loss with high‐intensity heat waves and overestimated yield loss with low‐intensity heat waves, thus supporting the influence of direct heat stress on reproductive processes in determining yield. These results have implications for rain‐fed cropping systems and point toward a climatic tipping point for soybean yield when future heat waves exceed optimum temperature.     

Temperature-sensitive gating in a descending visual interneuron, DCMD

Activity in neural circuits can be modified through experience-dependent mechanisms. The effects of high temperature on a locust visual interneuron (the descending contralateral movement detector, DCMD) have previously been shown to be mitigated by prior exposure to sub-lethal, elevated temperatures (heat shock, HS). Activity in the DCMD is reduced at high temperature in naïve animals (control), whereas HS animals show a maintained spike count at all temperatures. We examined whether this finding was due to direct effects of temperature on visual processing, or whether other indirect feedback mechanisms were responsible for the observed effect in the DCMD. Activity in the DCMD was elicited using a computer-generated looming image, and the response was recorded extracellularly. The temperature of visual processing circuits contributes directly to HS-induced plasticity in the DCMD, as maintaining the brain at 25°C during a thoracic temperature ramp eliminated the high frequency activity associated with HS. Removing ascending input by severing the thoracic nerve cord reduced DCMD thermosensitivity, indicating that indirect feedback mechanisms are also involved in controlling the DCMD response to increased thoracic temperature. Understanding how thermosensitive feedback within the locust affects DCMD function provides insight into critical regulatory mechanisms underlying visually-guided behaviors.     

Metabolic characteristics and oxidative damage to skeletal muscle in broiler chickens exposed to chronic heat stress

Emerging evidence has shown that acute heat exposure affects metabolic characteristics and causes oxidative damage to skeletal muscle in birds. Little is known, however, about such phenomena under chronic heat stress conditions. To address this, we designed the present study to determine the influence of cyclic (32 to 24 to 32 °C: 32 °C for 8 h/d, 32–24–32HS ), and constant (32 and 34 °C, 32HS and 34HS, respectively) heat exposure on the metabolic and peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat stress, particularly in the 32HS and 34HS groups, depressed feed intake and growth, while cyclic high temperature gave rise to a less severe stress response in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were enhanced (P < 0.05) by constant heat treatment; the degree of enhancement was not as large as the changes observed in our previous ‘acute’ heat stress model. The 3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS (citrate synthase) enzyme activities were lowered (P < 0.05) by both the cyclic and constant 34HS treatments, and constant 34HS group, respectively. These results suggest that chronic heat exposure decreases metabolic oxidation capacity in skeletal muscle of broiler chickens. On exposure to chronic heat stress, GPx activity remained relatively constant, though a temperature-dependent elevation in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was disturbed by the chronic stress condition. From these results it can be concluded that chronic heat stress did not induce oxidative damage to a major extent. This may probably be due to a decrease in metabolic oxidation capacity or due to a self-propagating scavenging system, though the system was not fully activated.     

Associations between glucocorticoids and sociality across a continuum of vertebrate social behavior

The causes and consequences of individual differences in animal behavior and stress physiology are increasingly studied in wild animals, yet the possibility that stress physiology underlies individual variation in social behavior has received less attention. In this review, we bring together these study areas and focus on understanding how the activity of the vertebrate neuroendocrine stress axis (HPA‐axis) may underlie individual differences in social behavior in wild animals. We first describe a continuum of vertebrate social behaviors spanning from initial social tendencies (proactive behavior) to social behavior occurring in reproductive contexts (parental care, sexual pair‐bonding) and lastly to social behavior occurring in nonreproductive contexts (nonsexual bonding, group‐level cooperation). We then perform a qualitative review of existing literature to address the correlative and causal association between measures of HPA‐axis activity (glucocorticoid levels or GCs) and each of these types of social behavior. As expected, elevated HPA‐axis activity can inhibit social behavior associated with initial social tendencies (approaching conspecifics) and reproduction. However, elevated HPA‐axis activity may also enhance more elaborate social behavior outside of reproductive contexts, such as alloparental care behavior. In addition, the effect of GCs on social behavior can depend upon the sociality of the stressor (cause of increase in GCs) and the severity of stress (extent of increase in GCs). Our review shows that the while the associations between stress responses and sociality are diverse, the role of HPA‐axis activity behind social behavior may shift toward more facilitating and less inhibiting in more social species, providing insight into how stress physiology and social systems may co‐evolve.