Current research in physiology最新文献

{"title":"From molecular to physical function: The aging trajectory","authors":"Tom A.H. Janssen ,&nbsp;Caroline V. Lowisz ,&nbsp;Stuart Phillips","doi":"10.1016/j.crphys.2024.100138","DOIUrl":"10.1016/j.crphys.2024.100138","url":null,"abstract":"<div><div>Aging is accompanied by a decline in muscle mass, strength, and physical function, a condition known as sarcopenia. Muscle disuse attributed to decreased physical activity, hospitalization, or illness (e.g. sarcopenia) results in a rapid decline in muscle mass in aging individuals and effectively accelerates sarcopenia. Consuming protein at levels above (at least 50–100% higher) the current recommended intakes of ∼0.8 g protein/kg bodyweight/d, along with participating in both resistance and aerobic exercise, will aid in the preservation of muscle mass. Physiological muscle adaptations often accompany the observable changes in physical independence an older adult undergoes. Muscle fibre adaptations include a reduction in type 2 fibre size and number, a loss of motor units, reduced sensitivity to calcium, reduced elasticity, and weak cross-bridges. Mitochondrial function and structure are impaired in relation to aging and are worsened with inactivity and disease states but could be overcome by engaging in exercise. Intramuscular connective tissue adaptations with age are evident in animal models; however, the adaptations in collagenous tissue within human aging are less clear. We know that the satellite muscle cell pool decreases with age, and there is a reduced capacity for muscle repair/regeneration. Finally, a pro-inflammatory state associated with age has detrimental impacts on the muscle. The purpose of this review is to highlight the physiological adaptations driving muscle aging and their potential mitigation with exercise/physical activity and nutrition.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100138"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related differences in the acute physiological response to a high-intensity CrossFit® workout","authors":"Manoel Rios ,&nbsp;Ricardo Cardoso ,&nbsp;Victor Machado Reis ,&nbsp;Daniel Moreira-Gonçalves ,&nbsp;David B. Pyne ,&nbsp;Ricardo J. Fernandes","doi":"10.1016/j.crphys.2025.100148","DOIUrl":"10.1016/j.crphys.2025.100148","url":null,"abstract":"<div><div>CrossFit® is popular form of fitness training but the cardiorespiratory, hemodynamic and metabolic responses have not been well characterised. We compared responses to a short Fran CrossFit® session (consisting of three rounds of 21, 15 and 9 front squat to press overhead and pull-ups) between sexes to evaluate differences in acute exercise effects. Twenty-five (15 males and 10 females) trained participants performed a prescribed Fran session at maximal exertion. Cardiorespiratory variables were assessed at baseline, during and post-exercise. The rating of perceived exertion, blood pressure, blood lactate and glucose concentrations were measured at baseline and in the recovery period. The males completed Fran session in less time (males 177 ± 15 vs females 206 ± 27 s; mean ± SD), resulting in higher peak oxygen uptake values (50.1 ± 3.3 vs 46.4 ± 2.2 mL kg ⁻¹ min ⁻¹), heart rate (187 ± 6 vs 180 ± 3 b min⁻¹) and percentage heart rate (96 ± 3 vs 93 ± 1 %) compared to females. In addition, elevated systolic blood pressure (male 154 ± 8 vs females 149 ± 10 mmHg), double product (27,050 ± 1504 vs 25,999 ± 2253 mmHg b∙min ⁻¹), blood lactate (15.7 ± 1.7 vs 14.6 ± 2.0 mmol L⁻¹) and glucose (132 ± 15 vs 132 ± 14 mg dL⁻¹) values were observed in both sexes post-exercise. The substantial metabolic demands associated with a Fran session can yield similar elevations in cardiorespiratory and hemodynamic responses in both sexes, meeting the criteria for developing cardiorespiratory fitness. Complementarily, these results suggest that researchers and coaches can use the Fran session at maximal effort to assess and monitor crossfitters' training status throughout a CrossFit® season, guiding efforts towards excellence in this demanding sport.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100148"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic effects of late-onset estradiol replacement in high-fat-fed ovariectomized mice","authors":"Alessandra Gonçalves da Cruz,&nbsp;Jessica Denielle Matos dos Santos,&nbsp;Ester dos Santos Alves,&nbsp;Anne Raissa Melo dos Santos,&nbsp;Bruna Fantini Trinca,&nbsp;Felipe Nunes de Camargo,&nbsp;Guilherme Fancio Bovolin,&nbsp;João Paulo Camporez","doi":"10.1016/j.crphys.2025.100144","DOIUrl":"10.1016/j.crphys.2025.100144","url":null,"abstract":"<div><h3>Background</h3><div>Decreased estrogen levels in postmenopausal women negatively impact metabolic health. It is known that estradiol (E2) replacement can reverse this condition. However, there is no consensus on whether the effects mediated by E2 depend on the starting time of E2 replacement after menopause. We aimed to investigate the effects of different onset E2 treatments on glucose tolerance and metabolic parameters in high-fat-fed ovariectomized mice.</div></div><div><h3>Material and methods</h3><div>Eight-week-old female C57BL/6J mice were divided into three groups: SHAM, OVX, and E2, to evaluate three different time points of E2 replacement after ovariectomy: early (after 4 weeks), intermediate (after 12 weeks), and late replacement (after 20 weeks). E2 groups received treatment through subcutaneous pellets.</div></div><div><h3>Results</h3><div>E2 replacement improved the parameters analyzed independently of the time since ovariectomy, reducing body weight gain and fat mass, as well as increasing the percentage of lean mass. Glucose intolerance, fasting insulin, HOMA-IR, and cholesterol levels were also reduced after treatment with E2. In the liver, there was a decrease in triacylglycerol (TAG) deposition, with no difference in the expression of SREBP1 and ERα proteins. In the muscle, there was a decrease in TAG deposition. In periuterine adipose tissue, there was an increase in the expression of SREBP1, FASN, and SCD, with no difference in the expression of ERα.</div></div><div><h3>Conclusions</h3><div>Our findings reinforce the critical role of E2 in regulating both glucose and lipid metabolism and indicate that E2 action on metabolic health was not dependent on time since ovariectomy for the parameters analyzed.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100144"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of the Quercetin on experimental cuprizone-induced multiple sclerosis in male C57BL/6 mice","authors":"Samin Ghasemi ,&nbsp;Shahin Hassanpour ,&nbsp;Razieh Hosseini","doi":"10.1016/j.crphys.2025.100146","DOIUrl":"10.1016/j.crphys.2025.100146","url":null,"abstract":"<div><div>This study aimed to determine protective effect of the Quercetin on experimental cuprizone-induced (CPZ) multiple sclerosis (MS) in Male C57BL/6 mice. Forty male C57BL/6 mice were allocated into 4 experimental groups. Control group received the standard diet. In group 2, mice received a diet containing 0.2 % (w/w) CPZ mixed with ground chow for a duration of 4 weeks (Zhu et al., 2021). In group 3, mice received Quercetin (150 mg/kg) orally every day for 4 weeks. In group 4, mice received a diet with 0.2 % CPZ and Quercetin (150 mg/kg) orally for 4 weeks. After incidence of the sign of the MS reflexive motor behavior and serum antioxidant levels were assessed. Based on the findings, administration of the CPZ significantly decreased ambulation score, number of crosses using OFT (open field test), stay on rotarod, hindlimb foot angle, front- and hindlimb suspension and grip strength (P &lt; 0.05). Quercetin significantly increased ambulation score, number of cross using, stay on rotarod, hindlimb foot angle, front- and hindlimb suspension and grip strength (P &lt; 0.05). Administration of the CPZ significantly increased serum malondialdehyde (MDA), tumor necrosis factor (TNF-α) and interleukin-1 beta (IL-1β) While decreased superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant status (TAS) levels (P &lt; 0.05). Quercetin significantly decreased serum MDA, TNF-α and IL-1β while increased SOD, GPX and TAS levels (P &lt; 0.05). These results suggested, Quercetin has protective effect against CPZ-induced MS in mice.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100146"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing laboratory education through collaborative online international learning: A case study between USA and UK students","authors":"Matthew Allan Jones ,&nbsp;Pika Miklavc ,&nbsp;MaryAnne Stewart","doi":"10.1016/j.crphys.2025.100141","DOIUrl":"10.1016/j.crphys.2025.100141","url":null,"abstract":"<div><div>Collaborative Online International Learning (COIL) has emerged in recent years as an effective and viable alternative to increase the international opportunities within taught curricula. Through recent innovations in online collaboration tools, and elevated demand for international opportunities, there has been a recent increase in the development of COIL opportunities globally across a range of health aligned disciplines. This style of learning has been described as positively contributing to the internationalisation of students and enhancement of their transferable skills. However, there have been no reported COIL opportunities described in the fields of laboratory medicine and biomedicine, likely due to the large practical elements associated with the subjects. This study therefore aims to develop a COIL opportunity that incorporates practical laboratory elements and evaluate the efficacy of this teaching and learning approach.</div><div>A laboratory-based COIL was developed and delivered across two days. Day one was composed of synchronous livestreamed laboratory demonstrations and practical activities, with day two focused on the completion of a time-dependent team-based task. The pedagogical impact of this laboratory-based COIL was evaluated through 1) pre and post surveys and 2) an overall survey utilising Likert scales.</div><div>The laboratory-based COIL was well received by students (n = 34) with the majority enjoying (94.1 %) and learnt a lot (94.1 %) by participating in the session. It also produced highly positive benefits to student confidence (97.1 %), teamworking (100 %), and communication (97.1 %). Pre (n = 46) and Post-analysis (n = 35) revealed significant enhancement of students international education knowledge, international medical practice knowledge, cultural intelligence, social initiative, emotional stability, and work-based flexibility (<em>P</em> &lt; 0.05). Further analysis based on participants international institution revealed significant differences in responses between the two participating cohorts, namely questions relating to cultural intelligence and their confidence of working with cultures unfamiliar to themselves.</div><div>We are the first to report that implementation of laboratory-based COIL opportunities have significant potential in enhancing students' international, cultural and transferable competencies within laboratory and health education. These findings suggest that practical-based COILs are effective methods for preparing students to thrive in a globalized healthcare environment, making a strong case for its continued use and expansion in educational programmes.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100141"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No sex differences in fatigability or neuromuscular responses during one set of maximal intended velocity muscle actions to failure at 30 % one-repetition maximum","authors":"Tyler J. Neltner ,&nbsp;Robert W. Smith ,&nbsp;Jocelyn E. Arnett ,&nbsp;Dolores G. Ortega ,&nbsp;Richard J. Schmidt ,&nbsp;Dona McCanlies ,&nbsp;Terry J. Housh","doi":"10.1016/j.crphys.2025.100149","DOIUrl":"10.1016/j.crphys.2025.100149","url":null,"abstract":"<div><div>Traditionally, research using dynamic constant external resistance (DCER) training has focused on self-selected velocities. This study aimed to examine sex differences in fatigability and neuromuscular responses during maximal intended velocity, DCER forearm flexion muscle actions to failure. Fourteen men (mean ± SD; age: 22.9 ± 2.0 yrs) and 13 women (age: 22.9 ± 2.6 yrs) completed one set of forearm flexion muscle actions to failure performing the concentric phase of the repetition at maximal intended velocity (as fast as possible). Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii. The results indicated that men were significantly stronger and more powerful than women, however, there were no sex differences in the number of repetitions to failure (70 ± 18) or reductions in peak force (31 ± 8 %), peak velocity (57 ± 18 %), or peak power (64 ± 17 %). Additionally, there were no sex differences in the neuromuscular responses, which included increases in EMG amplitude (AMP), decreases in EMG mean power frequency (MPF), and no changes in MMG AMP or MPF. The increase in EMG AMP and decrease in EMG MPF, combined with no changes in MMG AMP or MPF, suggested that the decreases in performance were due to excitation contraction coupling failure, rather than a reduction in central drive. Thus, despite the low relative load, the maximal intended velocity muscle actions resulted in similar impairments of contractile function for the men and women that diminished sex differences in fatigability.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100149"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the hypoglycemic effect of Cyanthillium cinereum (L.) H. Rob. and its dual impact on uterine contraction in gestational diabetic rats","authors":"Sasitorn Kerdsuknirund ,&nbsp;Arreeya Kosinan ,&nbsp;Panida Khunkaewla ,&nbsp;Pakanit Kupittayanant ,&nbsp;Pattama Tongdee ,&nbsp;Porntip Nimkuntod ,&nbsp;Susan Wray ,&nbsp;Sajeera Kupittayanant","doi":"10.1016/j.crphys.2025.100139","DOIUrl":"10.1016/j.crphys.2025.100139","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates the effects of <em>Cyanthillium cinereum</em> (L.) H. Rob. ethanolic extract (CCE) on gestational diabetes mellitus (GDM) in rats using biochemical, histological, and uterine contractility studies.</div></div><div><h3>Methods</h3><div>Diabetes was induced in pregnant rats using streptozotocin (60 mg/kg). CCE was administered orally at low (50 mg/kg BW) and high (500 mg/kg BW) doses from gestation day 7 to day 21. Maternal evaluations included body weight, gravid uterine weight, and biochemical assays for serum glucose, insulin, lipids, and liver enzymes. Fetal outcomes included fetal size. Histological analyses of maternal pancreatic and uterine tissues and uterine contractility studies using <em>ex vivo</em> muscle strip experiments were also performed.</div></div><div><h3>Results</h3><div>CCE and metformin (MET) significantly reduced elevated blood glucose levels and improved the Islets of Langerhans area compared to the GDM group (<em>P</em> &lt; 0.05). Both treatments showed a trend toward increased insulin levels (<em>P</em> &gt; 0.05) and significantly reduced lipids, AST, and ALP levels (<em>P</em> &lt; 0.05). High-dose CCE and MET increased gravid uterine weight and fetal size (<em>P</em> &lt; 0.05) while showing a trend toward reducing placental weight and index (<em>P</em> &gt; 0.05). Histological analysis revealed increased fiber area and decreased interstitial space in uterine sections (<em>P</em> &lt; 0.05). <em>Ex vivo</em>, CCE enhanced spontaneous and oxytocin-induced contractions (<em>P</em> &lt; 0.05), while MET had no effect.</div></div><div><h3>Conclusion</h3><div>CCE reduces elevated glucose levels and exhibits hypolipidemic and hepatoprotective effects, improving maternal and fetal outcomes in GDM. Its uterine contractility effects suggest potential as a complementary therapy to MET for GDM management.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100139"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143210956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the association between albuminuria and vascular health in individuals living with chronic kidney disease","authors":"Badal S.B. Pattar ,&nbsp;Sofia B. Ahmed ,&nbsp;Jessalyn K. Holodinsky ,&nbsp;Nicole Larsen ,&nbsp;Sakshi Kharbanda ,&nbsp;Sarah Rabi ,&nbsp;Victoria Riehl-Tonn ,&nbsp;Darlene Y. Sola ,&nbsp;Sarah Blayney ,&nbsp;Sandra M. Dumanski","doi":"10.1016/j.crphys.2025.100145","DOIUrl":"10.1016/j.crphys.2025.100145","url":null,"abstract":"<div><div>Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD). Albuminuria, a marker of CKD severity, is independently associated with cardiovascular disease, however limited studies explore the impact of sex. We aimed to explore sex differences in the association between albuminuria and vascular health in individuals living with CKD. Albuminuria was quantified through urine albumin-to-creatinine ratio (uACR) and measures of vascular health included Aortic Augmentation Index (AIx), Pulse Wave Velocity (PWV) and Mean Arterial Pressure (MAP). Multivariable linear regression analyses estimated the association between uACR and each outcome, and sex was assessed as an effect modifier. Adults living with CKD were recruited from nephrology clinics in Calgary, Canada and 66 participants (39 female, 27 male) were included in this study. A higher eGFR (89[56] versus 58[50] ml/min/1.73m2) and lower uACR (32[405] versus 386[933] mg/g) were observed in females. Sex modified the relationship between uACR and AIx; with a positive association in females (<span><math><mrow><mi>β</mi></mrow></math></span> = 0.02; p &lt; 0.01), and no relationship in males (<span><math><mrow><mi>β</mi></mrow></math></span> = -0.004; p = 0.16). Positive relationships between uACR and both PWV and MAP were observed, though sex did not modify either relationship. Further research to elucidate the mechanisms underpinning these sex differences are necessary to optimize and personalize cardiovascular risk reduction strategies in CKD.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100145"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acidosis enhances contribution of Ca2+-activated chloride channels to vascular tone regulation in early postnatal period","authors":"Anastasia A. Shvetsova ,&nbsp;Margarita A. Khlystova ,&nbsp;Valentina S. Shateeva ,&nbsp;Sofia D. Simonenko ,&nbsp;Anna A. Borzykh ,&nbsp;Denis V. Abramochkin ,&nbsp;Dina K. Gaynullina","doi":"10.1016/j.crphys.2025.100143","DOIUrl":"10.1016/j.crphys.2025.100143","url":null,"abstract":"<div><h3>Introduction</h3><div>Acidosis often occurs during clinical complications in newborns and can lead to changes in the mechanisms of arterial tone regulation. However, it is unknown how acidosis affects the activity of Ca²⁺-activated chloride channels (CaCC) in arteries during early ontogenesis. We hypothesized that their activity may increase during acidosis.</div></div><div><h3>Methods</h3><div>We studied isometric contractions of saphenous arteries isolated from adult and 10-13-day-old rats. Intracellular pH was measured using a fluorescent indicator BCECF-AM simultaneously with recording the contractile activity of the arterial preparation in isometric mode.</div></div><div><h3>Results</h3><div>Metabolic acidosis with pH = 6.8 caused a significant decrease in the arterial contractile responses of adult and 10-13-day-old rats. The functional contribution of CaCC was absent in the adult rat arteries both at pH = 7.4 and pH = 6.8. However, in 10-13-day-old rat pups, the functional contribution of CaCC was higher at pH = 6.8 compared to pH = 7.4.</div></div><div><h3>Conclusion</h3><div>Acidosis augments the functional role of CaCC in arteries during early postnatal ontogenesis, but not in adulthood.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100143"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1H MRS-based metabolite changes at ventral respiratory control centers of the medulla oblongata following administration of morphine in wild-type and GIRK2 mutant mice","authors":"Ozra Dehkordi ,&nbsp;Stephen Lin ,&nbsp;Safia Mohamud ,&nbsp;Richard M. Millis ,&nbsp;Paul C. Wang","doi":"10.1016/j.crphys.2025.100147","DOIUrl":"10.1016/j.crphys.2025.100147","url":null,"abstract":"<div><div>Respiratory depression is the leading cause of death in opioid overdose and is closely associated with the development of tolerance following repeated morphine use. However, the neurochemical adaptations in brainstem regions that regulate breathing, particularly under chronic opioid exposure, remain poorly understood. G-protein-gated inwardly rectifying potassium (GIRK) channels, especially the GIRK2 subunit, are expressed in rhythm-generating neurons of the pre-Bötzinger complex and have been implicated in opioid-induced respiratory depression. Nonetheless, their specific role in morphine-induced neurochemical changes is not yet fully defined. In this study, <em>in vivo</em> proton magnetic resonance spectroscopy (¹H MRS) was used in mice to assess morphine-induced metabolite changes in ventral brainstem regions encompassing the pre-Bötzinger complex. Wild-type mice were compared with GIRK2 heterozygous (GIRK2⁺/⁻) mutants. Baseline levels of several metabolites including glutamate (Glu), myo-inositol (Ins), N-acetylaspartate plus N-acetylaspartylglutamate (NAA + NAAG), and glutamate plus glutamine (Glu + Gln) differed significantly between GIRK2⁺/⁻ and wild-type mice. Despite these baseline differences, many of morphine's effects on metabolite levels were similar in the wild-type and GIRK2⁺/⁻ mice. Morphine increased phosphocreatine (PCr) in both genotypes, while total creatine (Cr + PCr) decreased only in the wild-type mice. Glutamine levels increased significantly in both groups. Notably, NAA decreased in wild-type but increased in GIRK2⁺/⁻ mice, whereas NAA + NAAG decreased in both. These findings demonstrate that chronic morphine exposure induces substantial neurochemical changes in brainstem respiratory centers. Although the GIRK2⁺/ ^- mutation altered some of the metabolite responses, it does not fully block morphine's effects, highlighting the complexity of opioid-induced adaptations in the respiratory control networks.</div></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"8 ","pages":"Article 100147"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}