American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Passive forearm stretching evokes robust and load-dependent muscle sympathetic nerve activity responses in humans.","authors":"Georgia C S Lehnen, Marcela S Araujo, Jhenny V Neri, Rosa V D Guerrero, Giovanna M R Cunha, Bruno M Silva, Gabriel S Trajano, Lauro C Vianna","doi":"10.1152/ajpregu.00021.2026","DOIUrl":"10.1152/ajpregu.00021.2026","url":null,"abstract":"<p><p>Muscle mechanoreflex has long been considered to make, at most, a minimal contribution to human sympathetic activation, as previous studies of passive exercise have typically reported absent, small, or transient responses. Whether passive stretching alone can elicit a sustained increase in muscle sympathetic nerve activity (MSNA), and whether such responses are dependent on mechanical load, remains unknown. We tested the hypothesis that passive forearm stretching is sufficient to activate the muscle mechanoreflex and provoke a load-dependent sympathetic response in healthy young adults. A total of 11 participants (9 men; 23 ± 4 yr) completed two sessions on separate days: an experimental session with five sets of 1-min passive forearm stretching, each separated by 15 s of rest, and an optional time-matched control session. MSNA was recorded via peroneal microneurography, whereas cardiovascular variables were continuously monitored (ECG, finger arterial pressure, and brachial sphygmomanometry). Passive stretching evoked robust increases in burst frequency (Δ10 ± 2.2 bursts·min^-1, <i>P</i> < 0.05), burst incidence (Δ16 ± 4.1 bursts·100 hb^-1, <i>P</i> < 0.05), and mean blood pressure (Δ10 ± 2.2 mmHg, <i>P</i> < 0.001). Torque during stretch was positively correlated with the change in burst incidence (<i>r</i> = 0.652, <i>P</i> = 0.029). Mechanoreflex-driven sympathoexcitation was accompanied by a rightward resetting of the spontaneous sympathetic baroreflex operating point, without alteration in reflex gain. All variables returned to baseline within 15-30 min of recovery. These findings provide the first direct evidence that passive forearm stretching elicits robust and sustained increases in MSNA in healthy humans, with responses exhibiting a clear load-dependent profile. Passive stretching thus emerges as a practical and physiologically robust model for probing mechanoreflex function and sympathetic regulation in humans.<b>NEW & NOTEWORTHY</b> This study provides the first direct evidence in humans, using microneurography, that passive forearm stretching elicits robust increases in sympathetic burst frequency and incidence. The positive association between torque and the magnitude of the sympathetic response highlights the load-dependent nature of muscle mechanoreceptor activation in shaping autonomic outflow. Together, these findings establish passive forearm stretching as a practical and physiologically robust model for investigating mechanoreflex function and human sympathetic regulation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R551-R560"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.","authors":"Sebastian F Salathe, Edziu Franczak, Zane Busick, Frederick B Boakye, Julie Allen, Andrew Lutkewitte, Heather Wilkins, John Thyfault, B A Kugler","doi":"10.1152/ajpregu.00031.2026","DOIUrl":"10.1152/ajpregu.00031.2026","url":null,"abstract":"<p><p>Menopause is linked to cognitive decline and reduced brain metabolism, whereas estrogen (E2) therapy has been shown to mitigate these effects. Understanding the molecular mechanisms by which ovarian hormones and E2 influence neuroprotection is essential for developing strategies to maintain brain health in women. In this study, we examined how the loss of ovarian hormones, with or without E2 treatment, affects the brain proteome and mitochondrial energy production in aged female C57BL/6J mice (36-40 wk). The mice underwent sham or ovariectomy (OVX) surgery and were fed a high-fat diet for 10 wk; 6 wk after surgery, OVX mice received either sesame oil or E2 treatment for 4 wk. Proteomic analysis of brain homogenates revealed 4,992 proteins regulated by E2, with pathway analysis showing increased signaling proteins related to synaptogenesis. OVX reduced proteins involved in synaptic function, branched-chain amino acid and ketone metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation (<i>Complexes I</i>, <i>IV</i>, and <i>V</i>), whereas E2 restored protein expression within these pathways. Despite alterations in OxPhos proteins, basal and <i>state 3</i> mitochondrial respiration remained unchanged, although notable impairments in <i>Complex IV</i> enzymatic activity were apparent in OVX, which were partially reversed by E2 treatment. Overall, these results indicate that E2 supports brain health by maintaining proteins crucial for synaptic integrity and metabolism, while partially offsetting the functional decline in mitochondrial bioenergetics associated with menopause.<b>NEW & NOTEWORTHY</b> The menopausal transition, marked by declining estrogen levels, alters cognition, neuroplasticity, and brain metabolism. Although hormone therapy benefits cognition, its molecular effects on the brain remain unclear. Using whole-brain proteomics in aged ovariectomized (OVX) mice with or without estrogen treatment, we found that OVX reduced proteins linked to synaptogenesis and mitochondrial metabolism. Estrogen reversed these declines, restoring pathways supporting neuronal signaling and energy balance, identifying estrogen-regulated proteins critical for maintaining brain health during menopause.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R489-R500"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal low-sodium diet impairs hippocampal neurogenesis and cognition in adult mouse offspring.","authors":"Xingrao Ke, Connie C Grobe, Justin L Grobe, Wei Yu, John J Reho, Kaela M Varberg, Robert H Lane, Jeffrey L Segar","doi":"10.1152/ajpregu.00304.2025","DOIUrl":"10.1152/ajpregu.00304.2025","url":null,"abstract":"<p><p>Sodium (Na) homeostasis is critical for organ and cell function. Although low maternal Na intake during gestation is associated with low offspring survival rates and birth weights, the long-term impact on neurocognitive function is not known. Identifying a relationship between perinatal Na dysregulation and adult behavioral and cognitive outcomes may be important given the prevalence of both dysnatremias and neurocognitive impairment in preterm infants. This study aimed to determine the association between maternal low Na intake (LSI) and hippocampal-dependent behaviors in mice. C57BL/6J dams were fed a standard (0.30%) or low (0.04%) Na diet from <i>postnatal day 0</i> until <i>postnatal day 21</i>, when pups were weaned onto a standard 2920x (0.15% Na) diet. Behavioral testing and hippocampal analyses were performed in adult mice at 60-80 days of age. Maternal LSI was associated with impaired spatial memory and learning and increased anxiety-like behaviors in offspring in a sex-specific manner. Maternal LSI impaired hippocampal neurogenesis and altered <i>Sox2</i> expression, downstream signaling, and epigenetic regulation. The magnitudes of these effects differed between sexes. Our findings suggest maternal LSI is sufficient to impair hippocampal development and cognitive functions in adult offspring.<b>NEW & NOTEWORTHY</b> An adverse perinatal environment results in increased risk of long-term health morbidity. Pregnancy and lactation are common times for women to alter their diets. Maternal low-sodium diet resulted in impaired offspring spatial memory and learning associated with hippocampal neurogenesis. Adequate maternal sodium intake is essential for neurodevelopment of offspring.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R463-R477"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological responses of individuals with idiopathic chilblains during cold exposure and rewarming: a nonrandomized clinical trial.","authors":"Areti K Kapnia, Konstantinos Mantzios, Panagiota Karanika, Elli V Angelopoulou-Athanatou, Panagiotis V Tsaklis, Andreas D Flouris","doi":"10.1152/ajpregu.00157.2025","DOIUrl":"10.1152/ajpregu.00157.2025","url":null,"abstract":"<p><p>Idiopathic chilblains (IC) is a localized inflammatory disorder affecting acral areas, with unclear pathophysiology and pathogenesis. This study aimed to investigate the vasomotor, autonomic, and inflammatory responses of adults with (HIC+) and without (HIC-) a history of IC during cold exposure and rewarming. Sixteen healthy adults (8 HIC+, 8 HIC-; 10 females, 6 males; aged 19-60 yr) underwent a controlled environmental protocol involving progressive cooling (22-10°C) followed by rewarming (22°C). Skin blood flow (SkBF); finger and toe temperatures (Tf and Tt); mean skin temperature (Tsk); microvascular oxygenation parameters including tissue saturation index (TSI), oxyhemoglobin (O₂Hb), and deoxyhemoglobin (HHb); and total blood volume (tHb) were recorded throughout. Serum cortisol, ferritin, vitamin D₃, antinuclear antibodies (ANAs), and scleroderma antibody (SCL-70) were also assessed. Compared to HIC- participants, the HIC+ group showed significantly lower SkBF (|<i>d</i>| = 0.43-0.56; <i>P</i> < 0.05) and Tf and Tt (|<i>d</i>| = 0.07-0.75) during cold exposure, along with reduced O₂Hb (|<i>d</i>| = 0.33 at 10°C) and increased HHb (|<i>d</i>| = 0.43-0.46 at 14 and 10°C), suggesting impaired oxygen delivery. No between-group differences were observed in TSI. During rewarming, SkBF (47.06 ± 54.94 vs. 22.69 ± 21.48 PU) and HHb levels (5.53 ± 3.64 vs. 3.07 ± 2.84 μM) in the right finger were higher in the HIC+ than the HIC- group (|<i>d</i>| = 0.35-0.54). No significant differences were observed in serum cortisol or thermal perception. No participants developed chilblains or acral symptoms during the 8-wk follow-up. These findings indicate that individuals with a history of IC exhibit heightened cold-induced vasoconstriction and peripheral microvascular hypoxia, which may underlie susceptibility to chilblains and nonfreezing cold injuries.<b>NEW & NOTEWORTHY</b> This is the first study to investigate the vascular and oxygenation responses to cold and rewarming conditions in otherwise healthy adults with a history of idiopathic chilblains. By combining controlled environmental exposure with thermophysiological assessment, the study identifies a hyperconstrictive-hypoxic microvascular phenotype. Future work should explore the role of adrenergic receptor polymorphisms and rewarming kinetics as potential modulators of vascular stress and therapeutic targets for preventing nonfreezing cold injuries.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R530-R536"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of pulmonary circulation, cardiac filling pressures, and sympathovagal balance in exercise-induced hyperventilation among cardiopulmonary disorders.","authors":"Marco Vicenzi, Gabriel Dias Rodrigues, Sergio Caravita, Gael Deboeck, Marinella Colombo, Irene Rota, Marta Mozzo, Gregorio Tersalvi, Eleonora Tobaldini, Stefano Carugo, Nicola Montano, Jean-Luc Vachiery, Philippe van de Borne","doi":"10.1152/ajpregu.00094.2025","DOIUrl":"10.1152/ajpregu.00094.2025","url":null,"abstract":"<p><p>Although chemosensitivity plays a role in exercise-induced hyperventilation in cardiopulmonary disorders, the integration of the underlying reflexes with cardiac hemodynamics is not fully understood. We aimed to explore the interplay between right- and left-heart pressure overload, right ventricular-pulmonary arterial (RV-PA) coupling, cardiovascular autonomic modulation, and ventilatory response in patients with cardiopulmonary disorders. Forty patients underwent echocardiography, cardiopulmonary exercise testing, and right heart catheterization. Spectral analysis of heart rate variability (HRV) was used to assess cardiovascular autonomic modulation of low- (LF) and high-frequency (HF) components, with LF/HF ratio as an index of sympathovagal interaction. Heart rate recovery (HRR) quantified vagal reactivation. RV-PA coupling was calculated through the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (PAPs) ratio, and V̇e/V̇co₂ slope defined ventilatory inefficiency. Patients were classified as NoPH (no pulmonary hypertension, <i>n</i> = 13), PCPH (precapillary pulmonary hypertension, <i>n</i> = 15), and LVDD (left ventricular diastolic dysfunction, <i>n</i> = 12). V̇e/V̇co₂ slope was higher in PCPH than LVDD and NoPH (53.9 vs. 43.7 vs. 42.2, <i>P</i> < 0.01). The LF/HF ratio was similar in PCPH and LVDD but higher in NoPH (<i>P</i> < 0.01), whereas HRR was significantly blunted in PCPH compared with LVDD and NoPH (<i>P</i> < 0.01). TAPSE/PAPs was significantly reduced in PCPH and LVDD vs. NoPH and was significantly correlated with all HRV parameters. Our findings support a tight interconnection between left- and right-heart hemodynamics, pulmonary circulation, sympathovagal control, and ventilatory response during exercise. Although additional mechanisms are involved, cardiopulmonary efficiency, captured by RV-PA coupling, emerges as a key determinant linking cardiopulmonary hemodynamics to autonomic modulation and ventilatory inefficiency.<b>NEW & NOTEWORTHY</b> The results underscore a multifaceted interaction among cardiopulmonary hemodynamics, right heart pressures, ventilatory response, and autonomic regulation. In particular, altered RV-PA coupling correlated with heightened sympathetic drive, indicating that cardiopulmonary efficiency and hemodynamics may influence central autonomic outputs. This suggests that mechanical stress or overload in the right heart could modulate sympathovagal balance, thereby contributing to altered autonomic responses during exercise in patients with cardiopulmonary disorders.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R480-R488"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single and repeat ischemic preconditioning unable to modify cold-induced vasodilation or cold air finger skin temperatures and manual dexterity.","authors":"Afton D Seeley, Phillip O Bodurtha, MariaLena A Shaw, David H Gonzalez Rojas, Shaun C Brazelton, Billie K Alba, John W Castellani","doi":"10.1152/ajpregu.00176.2025","DOIUrl":"10.1152/ajpregu.00176.2025","url":null,"abstract":"<p><p>Cold-induced peripheral vasoconstriction reduces skin blood flow, skin temperatures, and manual dexterity. This study proposed the use of single and repeated ischemic preconditioning (IPC) before cold exposure to <i>1</i>) improve peripheral skin temperatures, blood flow, and manual dexterity during 90 min of 0°C cold air exposure with exposed hands cold air (CA); <i>2</i>) enhance the cold-induced vasodilation (CIVD) response to 30 min of 8°C dual-hand water immersion and rewarming (CWI); and <i>3</i>) improve thermal perceptions during both exposures. Seventeen volunteers (16 males, 1 female) completed a repeated trial design: <i>1</i>) CON, no IPC; <i>2</i>) IPC1_A, one 40-min IPC procedure; <i>3</i>) IPC5, five consecutive days of IPC; and <i>4</i>) IPC1_B, one IPC procedure. Single IPC consisted of 4 × 5 min occlusion/5 min of reperfusion on the dominant arm. No dose of IPC, performed before cold tests, improved hand or finger skin temperatures, skin blood flow, manual dexterity, or thermal perceptions across 90 min spent in 0°C CA. No change in any CIVD or immediate rewarming parameter was demonstrated with IPC versus control. IPC5 improved nondominant hand thermal sensations compared with CON immediately upon immersion in 8°C water [median (min-max); IPC5: -2 (-3 to -1) arbitrary units (au), CON: -3 (-4 to -1) au, <i>P</i> = 0.045], with a similar trend in the dominant hand. Overall, neither one cycle of 4 × 5 min IPC nor five consecutive days of 4 × 5 min IPC appear capable of improving manual dexterity performance in 0°C cold air or indices of cold-induced vasodilation.<b>NEW & NOTEWORTHY</b> This investigation provides novel evidence that neither single nor repeated ischemic preconditioning can improve the neural cold-induced vasodilation response to cold water, augment cold water rewarming responses, or elevate hand and finger skin temperatures, skin blood flow, or manual dexterity in cold air.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R537-R550"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exaggerated systolic blood pressure response to late-night low- and high-intensity resistance exercise in healthy young men.","authors":"Amane Hori, Ryuji Saito, Kenichi Suijo, Masaki Mizuno, Norio Hotta","doi":"10.1152/ajpregu.00253.2025","DOIUrl":"10.1152/ajpregu.00253.2025","url":null,"abstract":"<p><p>Although resistance exercise (RE) is recommended for optimal health outcomes, it induces a marked acute elevation in blood pressure (BP). Cardiovascular functions exhibit diurnal variations. However, the impact of the time of day on the pressor response to RE remains poorly understood. Thus, we investigated the effect of time of day on BP response to dynamic RE. Ten healthy young men performed dynamic low [20% of a 1-repetition maximum (1RM)]- and high (70% 1RM)-intensity one-arm preacher curl followed by 2-min postexercise muscle ischemia (PEMI), which induces the metabolic component of the exercise pressor reflex. The sessions were conducted in the morning (08:00 AM), afternoon (04:00 PM), and late night (12:00 AM). Systolic BP responses to low- and high-intensity RE were significantly greater during the late night than in the morning or afternoon (low-intensity RE: morning, Δ0.1 ± 7.4 mmHg; evening, Δ0.6 ± 5.1 mmHg; late night, Δ6.7 ± 4.4 mmHg; high-intensity RE: morning, Δ18.2 ± 12.0 mmHg; evening, Δ16.5 ± 15.5 mmHg; and late night, Δ26.1 ± 9.7 mmHg, <i>P</i> ≤ 0.038). No significant difference was found in the pressor responses between the morning and afternoon (<i>P</i> ≥ 0.716). No significant effects of time of day on the pressor response to PEMI were observed (morning, Δ27.5 ± 11.7 mmHg; evening, Δ24.5 ± 13.8 mmHg; and late night, Δ29.9 ± 10.9 mmHg, <i>P</i> = 0.318). Our data suggest that the pressor response to dynamic RE increases during the late-night period compared with the daytime.<b>NEW & NOTEWORTHY</b> Determining the diurnal variation in the pressor response to resistance exercises is crucial for promoting safety. In this study, the systolic blood pressure response to low- and high-intensity dynamic resistance exercise was higher late at night than in the morning or afternoon in healthy young males. Our findings suggest that the pressor response to resistance exercise is heightened late at night. Therefore, the timing of exercise prescription may be considered in blood pressure management.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R501-R511"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive modeling of putamen dopamine in Parkinson's disease: relevance to prognosis, treatment, and prevention.","authors":"David S Goldstein","doi":"10.1152/ajpregu.00027.2026","DOIUrl":"10.1152/ajpregu.00027.2026","url":null,"abstract":"<p><p>Depletion of putamen dopamine (DA) characterizes Parkinson's disease (PD) and precedes the onset of motor symptoms by years. Increasing evidence implicates impaired vesicular sequestration and attenuated detoxification of the toxic catecholaldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL) in disease pathogenesis. We applied a mechanistic kinetic model to examine how perturbations in dopamine handling from DOPAL-induced autotoxicity affect the timing and trajectory of symptomatic PD. Using an icon-based application we constructed a model of intraneuronal dopamine synthesis, vesicular storage, leakage, metabolism, aldehyde detoxification, delayed toxicity, and α-synuclein modification. Model behavior was evaluated by internal consistency and concordance with empirical cellular, animal, imaging, and postmortem neurochemical data. We examined predicted effects of genetic variants, acquired factors (e.g., stress, environmental exposures), and treatments on vesicular dopamine content across the lifespan. Without imposing a predefined disease curve, the model generated a triphasic trajectory of vesicular dopamine loss-homeostasis, dyshomeostasis, and symptomatic decline-from delayed DOPAL-mediated toxicity, with progressive impairment of vesicular sequestration and other intraneuronal processes. The model predicted that genetic decreases in vesicular uptake or aldehyde detoxification and increases in dopamine biosynthesis would shorten the time to the onset of symptomatic disease, whereas monoamine oxidase inhibition, levodopa, and antioxidant treatment applied early and in combination would be protective. Preclinical, multitarget interventions would delay or prevent crossing a symptomatic threshold within the modeled lifespan. Systems modeling across the lifespan predicts a triphasic decline in putamen dopamine stores in PD. The timing and combination of interventions may be decisive for delaying or preventing symptomatic disease.<b>NEW & NOTEWORTHY</b> We used kinetic modeling to predict the temporal course of putamen dopamine depletion across the lifespan in Parkinson's disease and predict effects of autotoxicity, genetics, environmental exposures, and possible treatments on the timing of the onset of symptomatic disease.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R512-R529"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperphagia and hepatic lipid storage in ducks: an exploratory experimental model.","authors":"Laura-Lou Zwick, Chaïma Hakkach, Sandra Biasutti, Charlotte Andrieux, Jérôme Roy, Stéphane Panserat, Marianne Houssier","doi":"10.1152/ajpregu.00191.2025","DOIUrl":"10.1152/ajpregu.00191.2025","url":null,"abstract":"<p><p>This study aimed to investigate whether spontaneous hyperphagic behavior can be induced in mule ducks through a protocol combining feed restriction followed by 1-h concentrated meals and to assess the resulting hepatic metabolic responses. To achieve this, two protocols were tested. The first protocol initially demonstrated that a 5-day acclimation phase, consisting of alternating 23-h fasting periods and 1-h refeeding periods, was necessary to induce hyperphagia in ducks. Then, an increase in liver weight and glycogen content was measured up to 12 h after the substantial meal, before returning to baseline after 24 h, whereas total lipid levels remained unchanged. Based on these observations, a second protocol was designed to assess whether an additional meal provided 12 h after the last substantial meal could promote lipid storage in the liver. A significant increase in liver weight and glycogen content was measured after each 1-h meal, whereas total hepatic lipid content increased significantly after the last meal provided 12 h after the previous one. This was associated with an upregulation of genes involved in lipogenesis (<i>FASN</i>, <i>SCD1</i>, and <i>ELOVL6</i>) and carbohydrate oxidation (<i>HK1</i>), and a downregulation of a gene involved in lipid oxidation (<i>ACSL1</i>). Together, these results demonstrate for the first time that voluntary feeding alone can induce measurable hepatic lipid accumulation in mule ducks. This new protocol represents a valuable experimental model for the study of hepatic lipid metabolism in ducks and could contribute to the development of alternative strategies for liver fattening.<b>NEW & NOTEWORTHY</b> This study provides new insights into the physiological effects of a substantial voluntary meal on hepatic energy metabolism in the mule duck, a species for which information on this topic remains limited. Our findings show for the first time that hepatic lipid deposition can be induced through voluntary feeding, without the need for force-feeding. In the longer term, these results may support the development of alternative practices to force-feeding for foie gras production.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R451-R462"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher's note for Sá et al., volume 328, 2025, p. R481-R491.","authors":"","doi":"10.1152/ajpregu.00092.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajpregu.00092.2026_NOT","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"330 5","pages":"R563"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}