Physiological research最新文献

Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).

This review aims to describe a novel method in the field of electromyography (EMG), established and improved upon in the last three decades that is able to observe specific parameters of muscle units (MUs). This concept is called the decomposition method, based on its ability to decompose a surface EMG signal to describe muscle activity on the level of individual muscle units in contrast to the level of the whole muscle, as is customary for regular surface electromyography. We provide a brief overview of its history, constituent parts regarding both hardware and software and possible applications. We also acknowledge the state of the research, regarding the background of the decomposition algorithm, the main software component responsible for identifying individual motor units and their parameters. As a result of the ability to describe the behavior of individual motor units during muscle contractions, key concepts in neuromuscular physiology have been put forward, pertaining to the hierarchy of MUs during their recruitment. Together with the recent application for cyclic contractions and gait, the decomposition method is beginning to open up wider possibilities of enquiry.

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

We assessed the prognostic utility of the new perinephric fat adherence risk score - Mayo Adhesive Probability (MAP), in patients of East Asian ethnicity undergoing either laparoscopic partial nephrectomy (LPN) or laparoscopic radical nephrectomy (LRN). A retrospective analysis of clinical data was carried out on 169 patients who either underwent LPN or LRN surgery. These patients were categorized into two groups, group A (0-2 points) and group B (3-4 points) using the new MAP score. The overall clinical data between these two groups was compared and potential risk factors were investigated using logistic regression analyses. The new MAP score yielded an area under the curve of 0.761 (95 % CI: 0.691-0.831), indicating its effectiveness. Group B had a significantly higher incidence of adherent perirenal fat (APF) during surgery (p<0.001) and had a greater average age (p<0.001). There was an increased prevalence of hypertension (p=0.009), type 2 diabetes mellitus (p<0.001), and MAFLD (p<0.001) in group B. Additionally, there were significant differences in posterior perinephric fat thickness (p<0.05), lateral perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) between the two groups. The new MAP score holds significance in predicting APF in people of East Asian ethnicity undergoing LPN or LRN, and there is a strong correlation between elevated MAP scores and risk factors such as MAFLD and advanced age.

Aging is an inevitable and complex biological process that is associated with a gradual decline in physiological functions and a higher disease susceptibility. Omega-3 fatty acids, particularly docosahexaenoic acid, play a crucial role in maintaining brain health and their deficiency is linked to age-related cognitive decline. Combining omega-3-rich diets with exercise may enhance cognitive function more effectively, as both share overlapping neurobiological and physiological effects. This study aimed to evaluate the effect of exercise and omega-3 fatty acid (FA) supplementation in two different doses (160 mg/kg and 320 mg/kg) on anxiety-like behavior and cognitive abilities in both adult and aged rats. Male Wistar rats (4-5- and 23-24-month-old) were randomly divided into seven groups: 3-week control supplemented with placebo without exercise, low-dose omega-3 FAs, high-dose omega-3 FAs, 7-week control supplemented with placebo without exercise, exercise-only, low-dose omega-3 FAs with exercise, and high-dose omega-3 FAs with exercise. The administered oil contained omega-3 FAs with DHA:EPA in a ratio of 1.5:1. Our results indicate that aging negatively impacts the locomotor and exploratory activity of rats. In adult rats, a low dose of omega-3 FAs reduces locomotor activity when combined with exercise while high dose of omega-3 FAs reduces anxiety-like behavior and improves recognition memory when combined with exercise. The combination of omega-3 FAs and exercise had varying impacts on behavior, suggesting a need for further research in this area to fully understand their therapeutic efficacy in the context of cognitive changes associated with aging.

Cardiovascular diseases are the most important cause of morbidity and mortality in the civilized world. Stenosis or occlusion of blood vessels leads not only to events that are directly life-threatening, such as myocardial infarction or stroke, but also to a significant reduction in quality of life, for example in lower limb ischemia as a consequence of metabolic diseases. The first synthetic polymeric vascular replacements were used clinically in the early 1950s. However, they proved to be suitable only for larger-diameter vessels, where the blood flow prevents the attachment of platelets, pro-inflammatory cells and smooth muscle cells on their inner surface, whereas in smaller-diameter grafts (6 mm or less), these phenomena lead to stenosis and failure of the graft. Moreover, these polymeric vascular replacements, like biological grafts (decellularized or devitalized), are cell-free, i.e. there are no reconstructed physiological layers of the blood vessel wall, i.e. an inner layer of endothelial cells to prevent thrombosis, a middle layer of smooth muscle cells to perform the contractile function, and an outer layer to provide innervation and vascularization of the vessel wall. Vascular substitutes with these cellular components can be constructed by tissue engineering methods. However, it has to be admitted that even about 70 years after the first polymeric vascular prostheses were implanted into human patients, there are still no functional small-diameter vascular grafts on the market. The damage to small-diameter blood vessels has to be addressed by endovascular approaches or by autologous vascular substitutes, which leads to some skepticism about the potential of tissue engineering. However, new possibilities of this approach lie in the use of modern technologies such as 3D bioprinting and/or electrospinning in combination with stem cells and pre-vascularization of tissue-engineered vascular grafts. In this endeavor, sex-related differences in the removal of degradable biomaterials by the cells and in the behavior of stem cells and pre-differentiated vascular cells need to be taken into account. Key words: Blood vessel prosthesis, Regenerative medicine, Stem cells, Footprint-free iPSCs, sr-RNA, Dynamic bioreactor, Sex-related differences.

The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of physiological processes, since 1970. The review describes the first 35 years of the research mostly on the effect of light and daylength, i.e., photoperiod, on entrainment or resetting of the pineal rhythm in melatonin production and of intrinsic rhythms in the central biological clock. This clock controls pineal and other circadian rhythms and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. During the early chronobiological research, many original findings have been reported, e.g. on mechanisms of resetting of the pineal rhythm in melatonin production by short light pulses or by long exposures of animals to light at night, on modulation of the nocturnal melatonin production by the photoperiod or on the presence of high affinity melatonin binding sites in the SCN. The first evidence was given that the photoperiod modulates functional properties of the SCN and hence the SCN not only controls the daily programme of the organism but it may serve also as a calendar measuring the time of a year. During all the years, the chronobiological community has started to talk about "the Czech school of chronobiology". At present, the today´s Laboratory of Biological Rhythms of the Institute of Physiology CAS continues in the chronobiological research and the studies have been extended to the entire circadian timekeeping system in mammals with focus on its ontogenesis, entrainment mechanisms and circadian regulation of physiological functions. Key words: Pineal, Melatonin, AA-NAT rhythm, Light entrainment, Photoperiod, SCN clock.

N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors critical for synaptic transmission and plasticity, and for the development of neural circuits. Rare or de-novo variants in GRIN genes encoding NMDAR subunits have been associated with neurodevelopmental disorders characterized by intellectual disability, developmental delay, autism, schizophrenia, or epilepsy. In recent years, some disease-associated variants in GRIN genes have been characterized using recombinant receptors expressed in non-neuronal cells, and a few variants have also been studied in neuronal preparations or animal models. Here we review the current literature on the functional evaluation of human disease-associated variants in GRIN1, GRIN2A and GRIN2B genes at all levels of analysis. Focusing on the impact of different patient variants at the level of receptor function, we discuss effects on receptor agonist and co-agonist affinity, channel open probability, and receptor cell surface expression. We consider how such receptor-level functional information may be used to classify variants as gain-of-function or loss-of-function, and discuss the limitations of this classification at the synaptic, cellular, or system level. Together this work by many laboratories worldwide yields valuable insights into NMDAR structure and function, and represents significant progress in the effort to understand and treat GRIN disorders. Keywords: NMDA receptor , GRIN genes, Genetic variants, Electrophysiology, Synapse, Animal models.

Life manifests as growth, movement or heat production that occurs thanks to the energy accepted from the outside environment. The basis of energy transduction attracted the Czech researchers since the beginning of the 20th century. It further accelerated after World War II, when the new Institute of Physiology was established in 1954. When it was found that energy is stored in the form of adenosine triphosphate (ATP) that can be used by numerous reactions as energy source and is produced in the process called oxidative phosphorylation localized in mitochondria, the investigation focused on this cellular organelle. Although the Czech scientists had to overcome various obstacles including Communist party leadership, driven by curiosity, boldness, and enthusiasm, they characterized broad spectrum of mitochondrial properties in different tissues in (patho)physiological conditions in collaboration with many world-known laboratories. The current review summarizes the contribution of the Czech scientists to the bioenergetic and mitochondrial research in the global context. Keywords: Mitochondria, Bioenergetics, Chemiosmotic coupling.

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.