For many years, the response of the organism to decreased O2 concentrations in inhaled air has remained a subject of close attention for physicians and physiologists. Hypoxia can develop not only under extreme conditions—for example, during high altitudes—but also in everyday life: obstructive sleep apnea is a typical example. The respiratory system is one of the first to respond to oxygen deficiency. The signal of decreased O2 levels spreads throughout the organism via the circulatory system, affecting virtually all organs and tissues. In response to hypoxic exposure, multilevel adaptive responses are triggered: both local and systemic regulatory mechanisms are involved. At the local level, the vascular system plays a key role in providing tissues with O2—it regulates O2 delivery and its consumption by tissues. This review analyzes the specific features of local vascular tone regulation in various organs during acute hypoxia. Researchs demonstrates that in most hemodynamic regions of the systemic circulation, hypoxia causes vascular relaxation. This response is mediated through diverse mechanisms, particularly at the level of endothelial cells (through prostacyclin or nitric oxide) and smooth muscle cells. One of the key mechanisms of smooth muscle relaxation in response to hypoxia is the blockade of L-type Ca2+ channels, which is observed in the arteries of various organs in both humans and animals. Apparently, the contribution of various mechanisms to the effects of hypoxia on isolated vessels may be highly dependent on the severity of the hypoxic exposure, with the influence of some mechanisms replacing others as hypoxia increases.
Transcranial direct current stimulation (tDCS) is presently under intensive investigation as a potential method of analgesia. However, the specific mechanisms of tDCS action in different types of pain remain unclear. Recent studies suggest that prelimbic areas (PrL) may be involved in the therapeutic effects of tDCS in visceral pain. The aim of this study was to analyse the effects of tDCS over the medial prefrontal cortex (mPFC) on the background activity of PrL neurons and their reactivity to visceral nociceptive stimuli. The experiments were performed on anesthetized male Wistar rats. Anodal tDCS was delivered at 0.15 mA via a 3.5–4 mm2 electrode. Background activity of PrL neurons and their responses to nociceptive colorectal distension (CRD, 80 mmHg, 60 s) were recorded extracellularly using tungsten microelectrodes at fixed time points during 30-min tDCS and within an equal period after the stimulation. The results demonstrate that a single anodal tDCS over mPFC induces prolonged enhancement of background impulse activity in layer V PrL neurons and selectively increases their excitatory responses to CRD. The data suggest that PrL neurons can be targets for the tDCS analgesic action.
Bone marrow progenitor cells ensure the maintenance of hematopoiesis and bone tissue homeostasis. During spaceflight, they are exposed to microgravity and volatile organic compounds (VOCs), which are present in the atmosphere aboard a crewed spacecraft. While both factors are known to individually impair osteogenesis and hematopoiesis, their combined effects remain insufficiently studied. The aim of this study was to assess the functional state of bone marrow progenitor cells and bone tissue in Wistar rats under combined exposure to hindlimb unloading (HLU) and VOCs. The experiment employed a 14-day HLU model combined with inhalation exposure to a mixture of VOCs characteristic of the International Space Station atmosphere. We assessed the number of isolated bone marrow cells, clonogenic, proliferative, and differentiation potential of stromal progenitors, their paracrine and transcriptional activity, as well as the number of hematopoietic colony-forming units (CFUs). HLU and VOC co-exposure was found to decrease the number of fibroblast colony-forming units (CFU-F) in the bone marrow, reduce the division capacity of stromal progenitors, suppress their osteogenic potential, and enhance adipogenesis. A reduction in the number of erythroid and lymphoid hematopoietic CFUs was also observed. The exposure was accompanied by the formation of a pro-resorptive paracrine profile and pro-inflammatory activation of bone marrow and bone tissue cells. Transcriptional analysis revealed the upregulation of genes associated with bone matrix degradation and osteogenesis suppression, along with the downregulation of osteogenic commitment genes. Additionally, the downregulation of Cxcr4 and Cxcl12 gene expression was recorded, indicating a disruption of the bone marrow hematopoietic stem cell niche. Thus, the combined exposure to mechanical HLU and VOCs leads to a pro-resorptive shift in bone tissue homeostasis and altered regulation of hematopoiesis.
Aquaporin-9 (AQP9) channel protein levels were analyzed in the hypothalamus, cerebral cortex, and choroid plexus of the third ventricle of the brain in ground squirrels Spermophilus pigmaeus of both sexes during different phases of their life cycle (fall before entering hibernation, hibernation, and arousal from hibernation accompanied by an increase in body temperature to 25 and 37°C). Immunoblotting results demonstrate a significant increase in the level of this protein during hibernation (at a body temperature of 4°C) compared to the fall period (at a body temperature of 37°C) before hibernation. Upon an increase in body temperature to 25°C, a decrease in AQP9 optical density was noted in all the brain regions studied compared to the level during hibernation, whereas at 37°C, a statistically significant increase was noted only in the hypothalamus. These data demonstrate for the first time changes in the level of AQP9, which facilitates the diffusion of water and a number of neutral molecules (e.g., glycerol, urea, lactate) across the neuronal plasma membrane, during the period of extremely low temperature, as well as AQP9 dynamics during an increase in body temperature. Immunohistochemistry results confirm AQP9 expression in neurons of various brain regions in the ground squirrel and support the hypothesis of its adaptive function during hibernation.
Age is an important factor determining physiological stress resilience of humans and animals. The aim of this study was to characterize age-related differences in behavioral, endocrine, and metabolic responses to acute moderate stress in mature (9-month-old, 9S) compared to young (3-month-old sexually mature, 3S) male Wistar rats. The animals were exposed to stress once in a forced swim test in warm water, followed by behavioral assessment in the elevated plus maze (EPM). In the EPM test, 3S rats exhibited an avoidance response, characterized by decreased overall activity and an increased anxiety index (AI). In contrast, aged 9S rats demonstrated a pronounced activation of exploratory behavior, as evidenced by a higher locomotor activity and increased number of entries into the open arms of the EPM, along with a lower AI. These behavioral changes were accompanied by elevated circulating leptin levels, reduced ghrelin levels, and an improved redox system status. The specific reactivity observed in animals of this age may pose a high risk of distorting results in preclinical pharmacological trials. At the same time, this ontogenetic period holds considerable fundamental value for studying central nervous system activity and adaptation mechanisms, contributing to a deeper insight into age-related physiology and the development of age-oriented approaches.
