Mitochondrial Transplantation as a Novel Therapeutic Strategy for Mitochondrial Diseases

Mitochondria are the major source of intercellular bioenergy in the form of ATP. They are necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation of metabolism and apoptosis. Mitochondrial dysfunction has been observed in variety of diseases such as cardiovascular disease, aging, type 2 diabetes, cancer and degenerative brain disease. In other words, the interpretation and regulation of mitochondrial signals has the potential to be applied as a treatment for various diseases caused by mitochondrial disorders. In recent years, mitochondrial transplantation has increasingly been a topic of interest as an innovative strategy for the treatment of mitochondrial diseases by augmentation and replacement of mitochondria. In this review, we focus on diseases that are associated with mitochondrial dysfunction and highlight studies related to the rescue of tissue-specific mitochondrial disorders. We firmly believe that mitochondrial transplantation is an optimistic therapeutic approach in finding a potentially valuable treatment for a variety of mitochondrial diseases.

Menthol as an Ergogenic Aid for the Tokyo 2021 Olympic Games: An Expert-Led Consensus Statement Using the Modified Delphi Method

Introduction Menthol topical application and mouth rinsing are ergogenic in hot environments, improving performance and perception, with differing effects on body temperature regulation. Consequently, athletes and federations are beginning to explore the possible benefits to elite sport performance for the Tokyo 2021 Olympics, which will take place in hot (~ 31 °C), humid (70% RH) conditions. There is no clear consensus on safe and effective menthol use for athletes, practitioners, or researchers. The present study addressed this shortfall by producing expert-led consensus recommendations. Method Fourteen contributors were recruited following ethical approval. A three-step modified Delphi method was used for voting on 96 statements generated following literature consultation; 192 statements total (96/96 topical application/mouth rinsing). Round 1 contributors voted to “agree” or “disagree” with statements; 80% agreement was required to accept statements. In round 2, contributors voted to “support” or “change” their round 1 unaccepted statements, with knowledge of the extant voting from round 1. Round 3 contributors met to discuss voting against key remaining statements. Results Forty-seven statements reached consensus in round 1 (30/17 topical application/rinsing); 14 proved redundant. Six statements reached consensus in round 2 (2/4 topical application/rinsing); 116 statements proved redundant. Nine further statements were agreed in round 3 (6/3 topical application/rinsing) with caveats. Discussion Consensus was reached on 62 statements in total (38/24 topical application/rinsing), enabling the development of guidance on safe menthol administration, with a view to enhancing performance and perception in the heat without impairing body temperature regulation.

Body temperature maintenance acclimates in a winter-tenacious songbird

ABSTRACTFlexibility in heat generation and dissipation mechanisms provides endotherms the ability to match their thermoregulatory strategy with external demands. However, the degree to which these two mechanisms account for seasonal changes in body temperature regulation is unexplored. Here we present novel data on the regulation of avian body temperature to investigate how birds alter mechanisms of heat production and heat conservation to deal with variation in ambient conditions. We subjected Dark-eyed Juncos (Junco hyemalis) to chronic cold acclimations of varying duration and subsequently quantified their metabolic rates, thermal conductance, and ability to maintain normothermia. Cold-acclimated birds adjusted traits related to both heat generation (increased summit metabolic rate) and heat conservation (decreased conductance) to improve their body temperature regulation. Increases in summit metabolic rate occurred rapidly, but plateaued after one week of cold exposure. In contrast, changes to conductance occurred only after nine weeks of cold exposure. Thus, the ability to maintain body temperature continued to improve throughout the experiment, but the mechanisms underlying this improvement changed through time. Our results demonstrate the ability of birds to adjust thermoregulatory strategies in response to thermal cues and reveal that birds may combine multiple responses to meet the specific demands of their environments.

Formation of the “setting” level of body temperature regulation during endotoxin fever

The experiments on rats and rabbits using modern physiological, biochemical research methods and the pharmacological approach established that in the body, the action of bacterial endotoxin, accompanied by fever, leads to a significant decrease in blood plasma and in CSF of the arginine content. In rabbits after 30 min intravenous administration of carbon-labeled arginine hydrochloride (25 μCi/kg) at the endotoxin fever peak (after the 60 min injection of endotoxine E. coli), the radioactivity level in the blood plasma decreases and significantly increases in the cerebrospinal fluid and the hypothalamus tissue. It was revealed that although the content and speed of norepinephrine turnover in the hypothalamus after the introduction of L-arginine hydrochloride (100 μg) into the ventricles of the rats does not change in comparison with control animals, however, the chemoreactive properties of the thermoregulatory structures of the brain have changed, which manifests itself in the change in the expression and duration of thermoregulatory effects of the central action of norepinephrine and acetylcholine. It was established that the administration of L-arginine hydrochloride into the brain ventricles at a dose of 100 μg per animal or in the blood flow at a dose of 20 mg/kg caused the pronounced antipyretic effect. It was found that L-arginine hydrochloride (100 μg), after it has been introduced into the ventricles of the brain, increases the impulse activity of heat-sensitive neurons of the medial preoptic region of the anterior hypothalamus in rabbits due to a brain temperature growth when the animal’s body is overheated. Apparently, CSF arginine can be considered as an important factor in the changes in the excitability thresholds of cold and heat-sensitive neurons in the hypothalamus and in the formation of the “setpoint” of body temperature regulation during endotoxin fever.