Acta Physiologica最新文献

{"title":"Serotonergic input from the dorsal raphe nucleus shapes learning-associated odor responses in the olfactory bulb","authors":"Siqi Jing,&nbsp;Chi Geng,&nbsp;Penglai Liu,&nbsp;Dejuan Wang,&nbsp;Qun Li,&nbsp;Anan Li","doi":"10.1111/apha.14198","DOIUrl":"10.1111/apha.14198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Neural activity in the olfactory bulb (OB) can represent odor information during different brain and behavioral states. For example, the odor responses of mitral/tufted (M/T) cells in the OB change during learning of odor-discrimination tasks and, at the network level, beta power increases and the high gamma (HG) power decreases during odor presentation in such tasks. However, the neural mechanisms underlying these observations remain poorly understood. Here, we investigate whether serotonergic modulation from the dorsal raphe nucleus (DRN) to the OB is involved in shaping activity during the learning process in a go/no-go task in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fiber photometry was used to record the population activity of DRN serotonergic neurons during a go/no-go task. In vivo electrophysiology was used to record neural activity (single units and local field potentials) in the OB during the go/no-go task. Real-time place preference (RTPP) and intracranial light administration in a specific subarea (iClass) tests were used to assess the ability of mice to encoding reward information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Odor-evoked population activity in serotonergic neurons in the DRN was shaped during the learning process in a go/no-go task. In the OB, neural activity from oscillations to single cells showed complex, learning-associated changes and ability to encode information during an odor discrimination task. However, these properties were not observed after ablation of DRN serotonergic neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The activity of neural networks and single cells in the OB, and their ability to encode information about odor value, are shaped by serotonergic projections from the DRN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for direct CO2-mediated alterations in cerebral oxidative metabolism in humans","authors":"Hannah G. Caldwell,&nbsp;Ryan L. Hoiland,&nbsp;Anthony R. Bain,&nbsp;Connor A. Howe,&nbsp;Jay M. J. R. Carr,&nbsp;Travis D. Gibbons,&nbsp;Cody G. Durrer,&nbsp;Michael M. Tymko,&nbsp;Benjamin S. Stacey,&nbsp;Damian M. Bailey,&nbsp;Mypinder S. Sekhon,&nbsp;David B. MacLeod,&nbsp;Philip N. Ainslie","doi":"10.1111/apha.14197","DOIUrl":"10.1111/apha.14197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>How the cerebral metabolic rates of oxygen and glucose utilization (CMRO₂ and CMR_Glc, respectively) are affected by alterations in arterial PCO₂ (PaCO₂) is equivocal and therefore was the primary question of this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO₂ ranging between 30 and 60 mmHg. The CMRO₂ and CMR_Glc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CMRO₂ was altered by 0.5 mL × min⁻¹ (95% CI: −0.6 to −0.3) per mmHg change in PaCO₂ (<i>p</i> &lt; 0.001) which corresponded to a 9.8% (95% CI: −13.2 to −6.5) change in CMRO₂ with a 9 mmHg change in PaCO₂ (inclusive of hypo- and hypercapnia). The CMR_Glc was reduced by 7.7% (95% CI: −15.4 to −0.08, <i>p</i> = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: −11.2 to 0.06, <i>p</i> = 0.049) with a + 9 mmHg increase in PaCO₂.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, the CMRO₂ is altered by approximately 1% per mmHg change in PaCO₂. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO₂ are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indices of human heat stress in times of climate change","authors":"Shane K. Maloney,&nbsp;Michael R. Kearney,&nbsp;Duncan Mitchell","doi":"10.1111/apha.14196","DOIUrl":"10.1111/apha.14196","url":null,"abstract":"&lt;p&gt;Body temperature is one of the cardinal regulated variables in human physiology, along with blood gasses, pH, and osmolality. Pathological deviations of body temperature from normal, some potentially lethal, are becoming more likely with climate change. Sherwood and Huber&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; famously used a critical wet-bulb temperature that would cause pathology to project areas of the world that would become uninhabitable in a climate-changed future. Many other indices that incorporate the wet-bulb temperature have been advanced to predict human heat stress. As pointed out by Maloney,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; and recently confirmed empirically,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; those indices underestimate the impact of climate change on human thermoregulation, especially at lower humidity when physiological, rather than environmental, factors limit evaporative cooling (Figure 1).&lt;/p&gt;&lt;p&gt;Because the human body exchanges heat with the environment by four routes (conduction, convection, radiation, and evaporation), each impacted by different environmental variables, no single number can quantify that heat exchange accurately.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; But single numbers have nevertheless been proposed as indices of human heat stress. Because the dry-bulb temperature was poor at predicting the thermoregulatory responses of humans to different environments, in 1905 the English physiologist John Scott Haldane proposed the wet-bulb temperature as an alternative. The wet-bulb temperature is measured by placing a wetted sleeve over the bulb of a normal thermometer. Evaporation from the sleeve lowers the reading on the thermometer; the lower the humidity, the lower the reading of the wet-bulb thermometer below that of the normal thermometer. Wet-bulb temperature has been incorporated in many of the more than 150 indices of human thermal stress that have been developed over the past century.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; As well as underestimating the likelihood of pathology in some conditions, many of those indices also ignore the impact of air movement on both human heat exchange and on the wet-bulb temperature.&lt;/p&gt;&lt;p&gt;We all have been comforted by a breeze on a hot day, if we have been sweating. That effect has been quantified for acclimated women walking on a treadmill by measuring the upper limits of the prescriptive zone (ULPZ; that range of conditions in which core body temperature is affected by the level of metabolic heat production but not by the environment). In still air, the women could achieve heat balance in the conditions indicated by red shading below the dotted line in Figure 1. Conditions above that dotted line were above ULPZ, and the women became hyperthermic. At 1 ms&lt;sup&gt;−1&lt;/sup&gt; of forced air movement, their ULPZ increased to include the conditions indicated by dark-yellow shading below the solid line in Figure 1, so the ability of those women to avoid pathology improved. That improvement would not have been predicted by an index based on we","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multigenerational exposure to temperature influences mitochondrial oxygen fluxes in the Medaka fish (Oryzias latipes)","authors":"Julie Morla,&nbsp;Karine Salin,&nbsp;Rémy Lassus,&nbsp;Julie Favre-Marinet,&nbsp;Arnaud Sentis,&nbsp;Martin Daufresne","doi":"10.1111/apha.14194","DOIUrl":"10.1111/apha.14194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Thermal sensitivity of cellular metabolism is crucial for animal physiology and survival under climate change. Despite recent efforts, effects of multigenerational exposure to temperature on the metabolic functioning remain poorly understood. We aimed at determining whether multigenerational exposure to temperature modulate the mitochondrial respiratory response of Medaka fish.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multigenerational exposure with Medaka fish reared multiple generations at 20 and 30°C (COLD and WARM fish, respectively). We then measured the oxygen consumption of tail muscle at two assay temperatures (20 and 30°C). Mitochondrial function was determined as the respiration supporting ATP synthesis (OXPHOS) and the respiration required to offset proton leak (LEAK(Omy)) in a full factorial design (COLD-20°C; COLD-30°C; WARM-20°C; WARM-30°C).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that higher OXPHOS and LEAK fluxes at 30°C compared to 20°C assay temperature. At each assay temperature, WARM fish had lower tissue oxygen fluxes than COLD fish. Interestingly, we did not find significant differences in respiratory flux when mitochondria were assessed at the rearing temperature of the fish (i.e., COLD-20°C vs. WARM −30°C).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The lower OXPHOS and LEAK capacities in warm fish are likely the result of the multigenerational exposure to warm temperature. This is consistent with a modulatory response of mitochondrial capacity to compensate for potential detrimental effects of warming on metabolism. Finally, the absence of significant differences in respiratory fluxes between COLD-20°C and WARM-30°C fish likely reflects an optimal respiration flux when organisms adapt to their thermal conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing diuretic treatment of patients with edema and nephrotic syndrome","authors":"Gitte R. Hinrichs,&nbsp;Boye L. Jensen","doi":"10.1111/apha.14195","DOIUrl":"10.1111/apha.14195","url":null,"abstract":"&lt;p&gt;In the current issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Schork &lt;i&gt;et al.&lt;/i&gt; address a significant unresolved issue that puzzles researchers and challenges clinical decision-making, namely how to treat best edema associated with nephrotic syndrome (NS). NS is a kidney disorder with primary or secondary injury to the glomerular filtration barrier. NS is characterized by protein loss in urine above 3.5 g/d and generalized edema. Treatment of NS edema constitutes a therapeutic challenge. There is an unmet clinical need to evaluate the efficacy of diuretics and a need for better understanding of the pathogenesis as stated in Kidney Disease/Improving Global Outcome (KDIGO) 2021 guidelines on glomerular disease.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; By a gold-standard randomized approach, Schork &lt;i&gt;et al.&lt;/i&gt; compared the efficacy of the epithelial sodium channel (ENaC) blocker amiloride with the loop diuretic furosemide in adult patients with edema and NS. The primary endpoint was “overhydration” (OH) determined by non-invasive bioimpedance. Amiloride monotherapy was comparable to furosemide with similar reduction achieved in OH after 8 days. By testing these diuretic treatments, the authors provide further insight into the pathophysiological mechanism of salt retention known to reside in the tubular system.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The rationale for investigating amiloride, a theoretically weak diuretic compared to the more potent loop diuretic-class of drugs, is based on human studies demonstrating limited efficacy of volume correction with albumin infusion, renin-angiotensin system blockers and with furosemide. Preclinical studies in mice and rats with induced NS show that ENaC inhibitors mitigate sodium retention&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; although hormonal stimulators of ENaC, aldosterone, and angiotensin II, are unchanged or suppressed in plasma. The concept that ENaC may be activated by alternative pathways including proteolytic cleavage through soluble, extracellular, proteases present in tubular fluid in proteinuria has gained support. Not least the group of Schork &lt;i&gt;et al.&lt;/i&gt; has contributed significantly to this concept and published in &lt;i&gt;Acta Physiologica&lt;/i&gt; that the protease inhibitor aprotinin leads to natriuresis in mice with NS.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Intervention studies in patients with NS edema are limited. In pediatric patients, amiloride was as effective as furosemide and additive.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In adult patients with NS, amiloride (or its analogue triamterene) has been administered as a rational add-on for sequential blockade of Na&lt;sup&gt;+&lt;/sup&gt; transporters along the nephron&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; or as add-on in single patients with NS and resistant edema with remarkable, but casuistic, effect.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Schork &lt;i&gt;et al.&lt;/i&gt; show in adult patients with NS&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; that amiloride significantly reduced OH on Day 8, and both drugs did at Day 16 compared to","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut–immune axis during hypertension and cardiovascular diseases","authors":"Evany Dinakis,&nbsp;Joanne A. O'Donnell,&nbsp;Francine Z. Marques","doi":"10.1111/apha.14193","DOIUrl":"10.1111/apha.14193","url":null,"abstract":"<p>The gut-immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low-grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial-derived metabolites (e.g., short-chain fatty acids, trimethylamine <i>N</i>-oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater physical fitness (\u0000 \u0000 \u0000 \u0000 VO\u0000 \u0000 2\u0000 max\u0000 \u0000 \u0000 \u0000 ) in healthy older adults associated with increased integrity of the locus coeruleus–noradrenergic system","authors":"Emanuele R. G. Plini,&nbsp;Michael C. Melnychuk,&nbsp;Ralph Andrews,&nbsp;Rory Boyle,&nbsp;Robert Whelan,&nbsp;Jeffrey S. Spence,&nbsp;Sandra B. Chapman,&nbsp;Ian H. Robertson,&nbsp;Paul M. Dockree","doi":"10.1111/apha.14191","DOIUrl":"10.1111/apha.14191","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Vo&lt;/mi&gt;\u0000 &lt;msub&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mi&gt;max&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; – a measure of oxygen uptake and physical fitness (PF).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We hypothesized that greater &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Vo&lt;/mi&gt;\u0000 &lt;msub&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mi&gt;max&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;As hypothesized, greater &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Vo&lt;/mi&gt;\u0000 &lt;msub&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mi&gt;max&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This newly established link between &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments","authors":"Hasan Demirci,&nbsp;Suncica Popovic,&nbsp;Carsten Dittmayer,&nbsp;Duygu Elif Yilmaz,&nbsp;Ismail Amr El-Shimy,&nbsp;Michael Mülleder,&nbsp;Christian Hinze,&nbsp;Mingzhen Su,&nbsp;Philipp Mertins,&nbsp;Marieluise Kirchner,&nbsp;Bilgin Osmanodja,&nbsp;Alexander Paliege,&nbsp;Klemens Budde,&nbsp;Kerstin Amann,&nbsp;Pontus B. Persson,&nbsp;Kerim Mutig,&nbsp;Sebastian Bachmann","doi":"10.1111/apha.14190","DOIUrl":"10.1111/apha.14190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac). We aimed to study whether chronic CsA and Tac exposures, before reaching irreversible nephrotoxic damage, affect renal compartments differentially and whether related pathogenic mechanisms can be identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CsA and Tac were administered chronically in wild type Wistar rats using osmotic minipumps over 4 weeks. Functional parameters were controlled. Electron microscopy, confocal, and 3D-structured illumination microscopy were used for histopathology. Clinical translatability was tested in human renal biopsies. Standard biochemical, RNA-seq, and proteomic technologies were applied to identify implicated molecular pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both drugs caused significant albeit differential damage in vasculature and nephron. The glomerular filtration barrier was more affected by Tac than by CsA, showing prominent deteriorations in endothelium and podocytes along with impaired VEGF/VEGFR2 signaling and podocyte-specific gene expression. By contrast, proximal tubule epithelia were more severely affected by CsA than by Tac, revealing lysosomal dysfunction, enhanced apoptosis, impaired proteostasis and oxidative stress. Lesion characteristics were confirmed in human renal biopsies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that pathogenetic alterations in the renal compartments are specific for either treatment. Considering translation to the clinical setting, CNI choice should reflect individual risk factors for renal vasculature and tubular epithelia. As a step in this direction, we share protein signatures identified from multiomics with potential pathognomonic relevance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging","authors":"Pontus B. Persson,&nbsp;Philipp Hillmeister,&nbsp;Ivo Buschmann,&nbsp;Anja Bondke Persson","doi":"10.1111/apha.14192","DOIUrl":"10.1111/apha.14192","url":null,"abstract":"&lt;p&gt;A comprehensive understanding of the processes of aging is crucial for human health. From birth, we are subject to the effects of aging. However, it is only in later life that the physical effects of aging become apparent. Sociologically, age is often perceived as an advantage as we become wiser and more experienced. Physically, however, we lose functionality: hearing and vision deteriorate,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; muscles weaken,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; bones and joints wear out,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and diseases become more common. This raises the question of whether we age biologically as a result of disease, or whether the aging process itself is the cause. If the latter is the case, could aging, in the extreme, be considered a disease?&lt;/p&gt;&lt;p&gt;It is puzzling why closely related animal species age so differently. Some mammals, like mice, live for around 1 year, while others, like the bowhead whale, can live up to 200 years.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; What is certain is that our ability to regenerate decreases with age, and that aging and regeneration are linked: regeneration is optimal in the embryonic stage, acceptable in adulthood, and usually very poor in old age.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Different organisms exhibit varying regenerative potentials; for example, some lizards can simply regrow their limbs.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; What would be the implications of living more than 500 years and being able to regenerate from severe diseases and injuries? The Bible mentions Methuselah, who supposedly fathered Lamech at the age of 187 and lived for another 782 years (Old Testament (Gen 5:21–27)). Could humans theoretically achieve such longevity? If so, it would undoubtedly raise ethical issues. However, these considerations raise important questions about the biology of aging and the possibilities of regeneration, which are of great importance both to science and to our understanding of the human life cycle. Aging research has, in recent years, experienced transformative advances toward a deeper understanding of the molecular and cellular mechanisms of the aging process. Aging can be understood as a physiological process characterized by the degradation of biomolecules and the accumulation of damaged cellular components. As we age, the efficiency of mitochondrial function, critical for cellular energy production, diminishes, leading to a reduction in energy output; this decline is intricately connected to cellular senescence, where cells permanently halt division but remain viable, while telomere length, which shortens with age, is closely tied to cellular aging and senescence.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Aging is commonly perceived as a consequence of wear and tear, where accumulated damage over time leads to gradual physiological decline. Nevertheless, the notion of reverse aging, where exercise and interventions might rejuvenate tissues and restore youthful function, is gaining momentum, with research focusing on unraveling and manipul","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in the pathogenesis of chemotherapy-induced mucositis: Physiological mechanisms and therapeutic implications","authors":"Femke Heindryckx,&nbsp;Markus Sjöblom","doi":"10.1111/apha.14188","DOIUrl":"10.1111/apha.14188","url":null,"abstract":"<p>Chemotherapy is a common and effective treatment for cancer, but these drugs are also associated with significant side effects affecting patients' well-being. One such debilitating side effect is mucositis, characterized by inflammation, ulcerations, and altered physiological functions of the gastrointestinal (GI) tract's mucosal lining. Understanding the mechanisms of chemotherapy-induced intestinal mucositis (CIM) is crucial for developing effective preventive measures and supportive care. Chemotherapeutics not only target cancer cells but also rapidly dividing cells in the GI tract. These drugs disrupt endoplasmic reticulum (ER) homeostasis, leading to ER-stress and activation of the unfolded protein response (UPR) in various intestinal epithelial cell types. The UPR triggers signaling pathways that exacerbate tissue inflammation and damage, influence the differentiation and fate of intestinal epithelial cells, and compromise the integrity of the intestinal mucosal barrier. These factors contribute significantly to mucositis development and progression. In this review, we aim to give an in-depth overview of the role of ER-stress in mucositis and its impact on GI function. This will provide valuable insights into the underlying mechanisms and highlighting potential therapeutic interventions that could improve treatment-outcomes and the quality of life of cancer patients.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}