Journal of Physiology-London最新文献

{"title":"A sound vision: MYO7A gene therapy reaches the inner ear.","authors":"Shahar Taiber, Karen B Avraham","doi":"10.1113/JP290105","DOIUrl":"https://doi.org/10.1113/JP290105","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281603","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":"Molecular responses in abdominal subcutaneous adipose tissue after a session of endurance exercise: effects of exercise intensity.","authors":"Cheehoon Ahn, Tao Zhang, Thomas Rode, Gayoung Yang, Olivia K Chugh, Sierra Ellis, Sophia Ghayur, Shriya Mehta, Ryan Salzman, Hui Jiang, Stephen C J Parker, Charles F Burant, Jeffrey F Horowitz","doi":"10.1113/JP289339","DOIUrl":"https://doi.org/10.1113/JP289339","url":null,"abstract":"<p><p>The primary aim of this study was to compare the acute effects of three exercise intensities on abdominal subcutaneous adipose tissue (aSAT) transcriptome in regular exercisers. A total of 45 adults who exercise regularly were assigned to perform a single session of either low-intensity continuous (LOW; 60 min at 30% VO₂max; n = 15), moderate-intensity continuous (MOD; 45 min at 65% VO₂max; n = 15) or high-intensity interval exercise (HIGH; 10 × 1 min at 90% VO₂max interspersed with 1 min active recovery; n = 15). aSAT biopsy samples were collected before and 1.5 h after the exercise session for bulk RNA sequencing and targeted protein immunoassays. HIGH upregulated genes were involved in angiogenesis, protein secretion and insulin signalling pathways, whereas MOD and LOW upregulated genes regulated extracellular matrix (ECM) remodelling, ribosome biogenesis and oxidative phosphorylation pathways. Exercise-induced changes in aSAT clock genes, ERK protein phosphorylation and circulating cytokines were similar after all three exercise treatments. Network analysis identified exercise-responsive gene clusters linked to cardiometabolic health traits. Cell-type analysis highlighted a heterogeneous response of aSAT cell types to exercise, with distinct patterns observed across exercise intensities. Collectively, our data characterize early responses in aSAT after a single session of exercise. Because adaptations to exercise training stem from an accrual of responses after each session of exercise, these early responses to exercise are likely important contributors to the long-term structural and functional changes that occur in adipose tissue in response to exercise training. KEY POINTS: Chronic adaptations in adipose tissue from regular exercise support cardiometabolic health, but the acute molecular triggers of these adaptations remain unclear. We show that acute exercise alters gene expression, along with ERK phosphorylation in adipose tissue of regular exercisers. Exercise intensity shapes the transcriptomic response: high-intensity exercise induces inflammatory, cytokine and genes, whereas lower intensities upregulate genes involved in protein translation and oxidative phosphorylation. Network and cell-type analyses highlight intensity-specific adipose responses, revealing gene modules linked to health traits and differential engagement of adipocyte subpopulations.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281522","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":"Is the signal in the cells? Immune cell dynamics in the pathology of acute mountain sickness.","authors":"Erica C Heinrich","doi":"10.1113/JP289747","DOIUrl":"https://doi.org/10.1113/JP289747","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281533","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":"Anatomical and functional mapping of vagal nociceptive sensory nerve subsets innervating the mouse lower airways by intersectional genetics.","authors":"Mayur J Patil, Justin Shane Hooper, Seol-Hee Kim, Parmvir K Bahia, Nika Pavelkova, Sanjay S Nair, Teresa S Darcey, Karina V Lurye, Meghana Madaram, Jailene Fiallo, Stephen H Hadley, Thomas E Taylor-Clark","doi":"10.1113/JP289279","DOIUrl":"10.1113/JP289279","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Most vagal sensory afferents innervating the lower airways are activated by noxious stimuli including irritants (e.g. TRPV1 agonist capsaicin) and inflammatory mediators, causing nociceptive cardiorespiratory reflexes (e.g. cough, bronchospasm, changes in respiratory drive and heart rate). Vagal ganglia comprise embryologically distinct nodose and jugular neurons, but little is known of their specific contribution to nociceptive reflexes. Using a novel TRPV1&lt;sup&gt;Flp&lt;/sup&gt; mouse in combination with P2X2&lt;sup&gt;Cre&lt;/sup&gt;, Tac1&lt;sup&gt;Cre&lt;/sup&gt;, intersectional reporter mice, and adeno-associated virus we mapped and modulated distinct nociceptive afferents. TRPV1&lt;sup&gt;+&lt;/sup&gt;P2X2&lt;sup&gt;+&lt;/sup&gt; neurons were found exclusively in the nodose ganglion and were activated by αβmATP and capsaicin, but rarely expressed Tac1. TRPV1&lt;sup&gt;+&lt;/sup&gt;P2X2&lt;sup&gt;+&lt;/sup&gt; fibres innervated the lungs (many projected into the alveoli) but not the trachea. Centrally they innervated the nucleus tractus solitarius (nTS). More than 90% of TRPV1&lt;sup&gt;+&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt; neurons were found in the jugular ganglion and were activated by capsaicin but not αβmATP. TRPV1&lt;sup&gt;+&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt; fibres innervated the lungs (although none projected into the alveoli) and the trachea submucosa. They terminated solely in the paratrigeminal complex (Pa5). Many TRPV1&lt;sup&gt;-&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt; neurons were found in both nodose and jugular ganglia that innervated the trachea and large pulmonary airways. These projected to both nTS and Pa5. Using intersectional chemogenetics, we selectively stimulated lower airway afferent subsets using intravenous injections of clozapine-N-oxide. Activation of TRPV1&lt;sup&gt;+&lt;/sup&gt;, TRPV1&lt;sup&gt;+&lt;/sup&gt;P2X2&lt;sup&gt;+&lt;/sup&gt; or TRPV1&lt;sup&gt;+&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt; fibres evoked bradycardia and bradypnoea. Activation of Tac1&lt;sup&gt;+&lt;/sup&gt; fibres evoked tachycardia and tachypnoea. Activation of vagal TRPV1&lt;sup&gt;-&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt; neurons only evoked tachycardia. These data show the distinct innervation patterns and reflex function of multiple nociceptive vagal afferent subsets. KEY POINTS: Most sensory innervation of the lower airways is provided by vagal afferents, which are divided into distinct nodose and jugular subsets. Our intersectional approach showed that co-expression of P2X2 and TRPV1 labelled nodose nociceptors, that co-expression of Tac1 and TRPV1 labelled jugular nociceptors, and that Tac1 expression with TRPV1 labelled a mixed population of nodose and jugular neurons. Nodose nociceptors, jugular nociceptors and vagal TRPV1-negative Tac1-positive (TRPV1&lt;sup&gt;-&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt;) afferents project to distinct medulla subnuclei, and innervate different regions and tissues within the lower airways. Chemogenetic activation (via intravenous clozapine-N-oxide) of nodose and jugular nociceptors evoked bradypnoea and bradycardia, whereas activation of TRPV1-negative Tac1-positive (TRPV1&lt;sup&gt;-&lt;/sup&gt;Tac1&lt;sup&gt;+&lt;/sup&gt;) afferents evoked tachycardia. These data show t","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281576","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":"Excitatory neurotransmission at O₂ receptors in zebrafish gill: It takes two to tango.","authors":"Colin A Nurse, Erin M Leonard","doi":"10.1113/JP290062","DOIUrl":"https://doi.org/10.1113/JP290062","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281570","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":"Post-exercise hot water immersion: A potential lifestyle strategy to maximize vascular health.","authors":"Jin-Su Kim, Eui-Young Lee","doi":"10.1113/JP289836","DOIUrl":"https://doi.org/10.1113/JP289836","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281587","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":"The what, which, when, why and who of Off responses in the auditory system.","authors":"Jean-Marc Edeline, Robert C Liu","doi":"10.1113/JP289100","DOIUrl":"https://doi.org/10.1113/JP289100","url":null,"abstract":"<p><p>For decades, the Off responses noted in the auditory system from the cochlear nucleus up to the secondary auditory cortex have been largely ignored. Over the last few years, several studies have reinvigorated interest in Off responses in the auditory system and described their cellular mechanisms and the plasticity they display during various behaviours. While it is possible to design tasks where Off responses are necessary for an animal's behavioural performance, we posit that it is the interplay of On and Off responses that the brain uses more generally to enable sound feature perception, including sound duration and sound offset detection. Moreover, based upon close examination of the latencies and durations of published Off responses, we propose here that two different types of Off responses should be considered. We suggest that short latency-short duration responses participate in the neural coding of acoustic parameters whose estimates cannot be obtained on the sole basis of onset features. Meanwhile, long latency-long duration responses potentially reflect more cognitive variables associated with the learned use of a particular stimulus in a behavioural context. Proposing two varieties of Off responses draws attention to the need to better characterize post-stimulus firing in future studies to more definitively distinguish divergent mechanisms.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276361","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":"Special issue: The giant impact of synapses on brain function and disease.","authors":"Samuel M Young, Lu-Yang Wang","doi":"10.1113/JP289770","DOIUrl":"https://doi.org/10.1113/JP289770","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259875","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":"Redefining human heat limits: integrating molecular and evolutionary physiology.","authors":"Abderrezak Bouchama","doi":"10.1113/JP289455","DOIUrl":"https://doi.org/10.1113/JP289455","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276307","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":"Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission.","authors":"Daniele Ferrante, Barbara Parisi, Antonella Marte, Dionisi Marianna, Cosimo Prestigio, Andrea Benzi, Santina Bruzzone, Fabio Benfenati, Franco Onofri, Pierluigi Valente, Pietro Baldelli","doi":"10.1113/JP288763","DOIUrl":"https://doi.org/10.1113/JP288763","url":null,"abstract":"<p><p>Under resting conditions most neuronal ATP is produced through mitochondrial oxidative phosphorylation, whereas glycolysis becomes more important during intense neuronal firing. Recent studies suggest that inhibiting glycolysis plays a key role in regulating seizure-related hyperactivity, with the epigenetic modulator REST/NRSF being activated when glycolysis inhibition lowers the NADH/NAD⁺ ratio. Our previous research has shown that REST/NRSF initiates homeostatic processes to counteract neuronal hyperactivity by regulating both firing and synaptic activities. However, the exact mechanism through which the metabolic activation of REST/NRSF controls neuronal excitability is still unknown. Here, we studied the role of REST/NRSF in the effects of glycolysis inhibition on hippocampal neuron activity. Treatment with 2-deoxy-d-glucose (2DG) decreased the NADH/NAD⁺ ratio, increased REST/NRSF expression, and promoted its nuclear translocation. Although GABAergic inhibitory inputs and the firing properties of both excitatory and inhibitory neurons were unaffected by 2DG, the amplitude of evoked EPSCs (eEPSCs) and miniature EPSCs (mEPSCs) was reduced in a REST/NRSF-dependent manner. This effect was associated with a REST/NRSF-dependent reduction in the size of GluA2-positive puncta and a decrease in GluA2 expression in the absence of changes in the density of excitatory synapses. These effects provide a mechanistic basis for the significant reduction in network firing and bursting activity observed when the hippocampal network was treated with 2DG. These findings highlight a role of the REST/NRSF-dependent pathway in the 2DG-mediated downregulation of excitatory inputs, a mechanism that contributes to neuronal network stability, strengthening the homeostatic defences against hyperactivity. KEY POINTS: Reducing glucose metabolism with 2-deoxy-d-glucose (2DG) lowers the cell's energy balance and increases the levels of a gene regulator called REST/NRSF. REST/NRSF then moves into the nucleus, where it controls the activity of genes linked to nerve cell communication. 2DG weakens the strength of signals between excitatory nerve cells, without affecting inhibitory signals or the basic ability of neurons to fire. This effect depends in part on REST/NRSF, which reduces the amount and size of GluA2-containing AMPA receptors at excitatory synapses, without altering the overall number of excitatory contacts. These findings suggest that blocking glucose metabolism activates a protective response that stabilizes brain networks, which could help control seizures in epilepsy.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276301","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}