Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse

Background: Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA. Objectives: To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs?. Methods: Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry. Results: Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP+ nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed. Conclusions: These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate ‘HF-IP guardian’ that may be therapeutically exploited to inhibit the progression of AA lesions.</p

Communally breeding bats use physiological and behavioural adjustments to optimise daily energy expenditure

Small endotherms must change roosting and thermoregulatory behaviour in response to changes in ambient conditions if they are to achieve positive energy balance. In social species, for example many bats, energy expenditure is influenced by environmental conditions, such as ambient temperature, and also by social thermoregulation. Direct measurements of daily fluctuations in metabolic rates in response to ambient and behavioural variables in the field have not been technologically feasible until recently. During different reproductive periods, we investigated the relationships between ambient temperature, group size and energy expenditure in wild maternity colonies of Bechstein’s bats (Myotis bechsteinii). Bats used behavioural and physiological adjustments to regulate energy expenditure. Whether bats maintained normothermia or used torpor, the number of bats in the roosts as well changed with reproductive status and ambient temperature. During pregnancy and lactation, bats remained mostly normothermic and daily group sizes were relatively large, presumably to participate in the energetic benefits of social thermoregulation. In contrast, smaller groups were formed on days when bats used torpor, which occurred mostly during the post-lactation period. Thus, we were able to demonstrate on wild animals under natural conditions the significance of behavioural and physiological flexibility for optimal thermoregulatory behaviour in small endotherms

Ambient Temperature Cycles Affect Daily Torpor and Hibernation Patterns in Malagasy Tenrecs.

Hibernation and daily torpor (heterothermy) allow endotherms to cope with demanding environmental conditions. The depth and duration of torpor bouts vary considerably between tropical and temperate climates, and tropical hibernators manage to cope with a wider spectrum of ambient temperature (Ta) regimes during heterothermy. As cycles in Ta can have profound effects on activity and torpor patterns as well as energy expenditure, we examined how these characteristics are affected by daily fluctuating versus constant Ta in a tropical hibernator, the lesser hedgehog tenrec (Echinops telfairi). Throughout the study, regardless of season, the tenrecs became torpid every day. In summer, E. telfairi used daily fluctuations in Ta to passively rewarm from daily torpor, which led to synchrony in the activity phases and torpor bouts between individuals and generally decreased energy expenditure. In contrast, animals housed at constant Ta showed considerable variation in timing and they had to invest more energy through endogenous heat production. During the hibernation season (winter) E. telfairi hibernated for several months in constant, as well as in fluctuating Ta and, as in summer, under fluctuating Ta arousals were much more uniform and showed less variation in timing compared to constant temperature regimes. The timing of torpor is not only important for its effective use, but synchronization of activity patterns could also be essential for social interactions, and successful foraging bouts. Our results highlight that Ta cycles can be an effective zeitgeber for activity and thermoregulatory rhythms throughout the year and that consideration should be given to the choice of temperature regime when studying heterothermy under laboratory conditions

Open-flow respirometry under field conditions: How does the airflow through the nest influence our results?

Open-flow respirometry is a common method to measure oxygen-uptake as a proxy of energy expenditure of organisms in real-time. Although most often used in the laboratory it has seen increasing application under field conditions. Air is drawn or pushed through a metabolic chamber or the nest with the animal, and the O2 depletion and/or CO2 accumulation in the air is analysed to calculate metabolic rate and energy expenditure. Under field conditions, animals are often measured within the microclimate of their nest and in contrast to laboratory work, the temperature of the air entering the nest cannot be controlled. Thus, the aim of our study was to determine the explanatory power of respirometry in a set-up mimicking field conditions. We measured O2 consumption of 14 laboratory mice (Mus musculus) using three different flow rates [50 L*h−1 (834 mL*min−1), 60 L*h−1 (1000 mL*min−1) and 70 L*h−1 (1167 mL*min−1)] and two different temperatures of the inflowing air; either the same as the temperature inside the metabolic chamber (no temperature differential; 20 °C), or cooler (temperature differential of 10 °C). Our results show that the energy expenditure of the mice did not change significantly in relation to a cooler airflow, nor was it affected by different flow rates, despite a slight, but significant decrease of about 1.5 °C in chamber temperature with the cooler airflow. Our study emphasises the validity of the results obtained by open-flow respirometry when investigating energy budgets and physiological responses of animals to ambient conditions. Nevertheless, subtle changes in chamber temperature in response to changes in the temperature and flow rate of the air pulled or pushed through the system were detectable. Thus, constant airflow during open-flow respirometry and consequent changes in nest/chamber temperature should be measured

Modelling mammalian energetics: the heterothermy problem

Global climate change is expected to have strong effects on the world’s flora and fauna. As a result, there has been a recent increase in the number of meta-analyses and mechanistic models that attempt to predict potential responses of mammals to changing climates. Many models that seek to explain the effects of environmental temperatures on mammalian energetics and survival assume a constant body temperature. However, despite generally being regarded as strict homeotherms, mammals demonstrate a large degree of daily variability in body temperature, as well as the ability to reduce metabolic costs either by entering torpor, or by increasing body temperatures at high ambient temperatures. Often, changes in body temperature variability are unpredictable, and happen in response to immediate changes in resource abundance or temperature. In this review we provide an overview of variability and unpredictability found in body temperatures of extant mammals, identify potential blind spots in the current literature, and discuss options for incorporating variability into predictive mechanistic models

Flexibility in thermal physiology and behaviour allows body mass maintenance in hibernating hazel dormice

Studying animals under natural or semi‐natural conditions is essential to better understand the implications of a warming climate on species survival. Here, we provide evidence of the effects of increasing winter ambient temperature (Ta) on the thermal physiology, feeding behaviour and body mass (BM) of a small mammalian hibernator, the hazel dormouse Muscardinus avellanarius. We collected skin temperature, metabolic rate (MR) and BM data from captive, hibernating dormice exposed to two winters of differing intensity in outdoor aviaries. Additionally, we obtained skin temperature data from one free‐ranging individual during the hibernation period. Statistical modelling showed that Ta and time since the start of hibernation both had significant non‐linear effects on the probability of arousal from torpor. During the warmer winter (Ta&lt;0°C on 26 days), foraging resulted in higher BMs for some individuals, despite more frequent arousals, than during the colder winter (Ta&lt;0°C on 86 days). As expected, Ta had a non‐linear effect on MR during torpor, with the lowest energy expenditure at intermediate Ta, and normothermic MR was minimal when Ta was warmer. The negative effect of increased arousal frequency on BM was counteracted by the positive effect of foraging on BM. Conforming with the accumulating body of evidence on high flexibility in physiological responses in many small mammals, we found that the thermoregulatory and behavioural responses of dormice during hibernation were more flexible than previously observed for this temperate, fat‐storing species. The ability to respond to prevailing environmental conditions might help M. avellanarius cope with increasing winter Ta predicted for ongoing global warming