Impact of cold exposure duration and intensity on hippocampal tyrosine hydroxylase, brain-derived neurotrophic factor, and mitochondrial markers in mice

Cold exposure brings systemic benefits to the body, including neuroprotection. Nevertheless, cold exposure remains a stressor to the body and may have adverse effects if applied excessively. Our study aimed to examine four different stimuli of cold water immersion, to verify whether repeated cold-water immersion might trigger positive adaptive responses in the hippocampus of mice. Mice were immersed in 4 °C water five times per week for four weeks. The groups of mice were differentiated by the time of immersion (three/six minutes) and the volume of the immersed body (partial/whole). Despite a similar increase in blood corticosterone concentration, measured immediately after 10th and 20th cold exposure, in all cold-exposed groups, we observed altered tyrosine hydroxylase (TH), brain-derived neurotrophic factor (BDNF), cytochrome c oxidase subunit I, A kinase anchor protein 1 (AKAP1), and other signalling proteins in the hippocampus. Our results suggest that properly administered, repeated cold exposure may be neuroprotective. The body's response and the activation of signalling pathways depend on the duration of the cold exposure. BDNF signalling is activated upon weaker stimuli, while IGF-1 is activated under overload stress conditions. The intermediate stimulation intensity increases TH protein content in the hippocampus, alongside the rise of the content of mitochondrial markers. These findings demonstrate the complex interplay between cold stress, hippocampal signalling, and neuroprotective mechanisms, with implications for understanding the brain's response to environmental stressors.