Involvement of neurogenomic regulation in maintenance of temperature homeostasis in the cold

Abstract

We present data from several studies that indicate the important role of the genome in the regulation of temperature homeostasis. Long-term adaptation to cold causes specific changes in the expression of genes for thermosensitive TRP ion channels (TRPV3) and serotonin receptors (5HT-2A) in the hypothalamus. These changes are specific for the hypothalamus, the center of thermoregulation, and they are not observed in other parts of the brain. This may indicate that adaptive changes in the thermal sensitivity of hypothalamic neurons involve at least two adaptive genomic mechanisms, which regulate the ratio between thermosensitive TRP ion channels and mediator receptors located in a neuron. These two mechanisms can complement each other. With regard to the important role of ion channel TRPM8 in the formation of colddefense thermoregulatory, metabolic, and immune responses, it is reasonable to assume that variations in the functioning of the ion channel lead to the formation of diverse individual defense responses to environmental changes. Studies on humans provide evidence for the role of the rs11562975 single nucleotide polymorphism in the TRPM8 gene in the variability of temperature perception and, consequently, in the development of the cold defense response. Individuals with the heterozygous GC genotype are more sensitive to the cold and less sensitive to menthol (agonist of the TRPM8 ion channel) as compared to people with the homozygous GG genotype. In addition, this polymorphism results in a less energy-consuming hypometabolic response to cooling.