{"title":"The origin of myocardial passive stiffness: more than the sum of its parts?","authors":"Martina Krüger","doi":"10.1007/s00424-024-02936-x","DOIUrl":"10.1007/s00424-024-02936-x","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The renin angiotensin aldosterone system.","authors":"Hannah Triebel, Hayo Castrop","doi":"10.1007/s00424-024-02908-1","DOIUrl":"10.1007/s00424-024-02908-1","url":null,"abstract":"<p><p>In this review, we will cover (i) the proteolytic cascade of the RAAS, (ii) its regulation by multiple feedback-controlled parameters, and (iii) the major effects of the RAAS. For the effects of the RAAS, we focus on the role of the RAAS in the regulation of volume homeostasis and vascular tone, as major determinants of arterial blood pressure.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dingding Lv, Bin Xiao, Huaying Liu, Linping Wang, Yingshun Li, Yin Hua Zhang, Qinghua Jin
{"title":"Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats.","authors":"Dingding Lv, Bin Xiao, Huaying Liu, Linping Wang, Yingshun Li, Yin Hua Zhang, Qinghua Jin","doi":"10.1007/s00424-024-02924-1","DOIUrl":"10.1007/s00424-024-02924-1","url":null,"abstract":"<p><p>Obesity has been linked with the impairment of spatial memory and synaptic plasticity but the molecular mechanisms remained unidentified. Since glutamatergic transmission and NMDA receptor neural pathways in hippocampal dentate gyrus (DG) are essential in the learning and memory, we aimed to investigate glutamate (Glu) and NMDA receptor signaling of DG in spatial learning and memory in diet-induced obesity (DIO) rats. Spatial learning and memory were assessed via Morris water maze (MWM) test on control (Ctr) and DIO rats. Extracellular concentration of Glu in the DG was determined using in vivo microdialysis and HPLC. The protein expressions of NMDA receptor subunit 2B (NR2B), brain-derived neurotrophic factor (BDNF), the activation of calcium/calmodulin-dependent kinase II (CaMKII) and cAMP-response-element-binding protein (CREB) in the DG were observed by western blot. Spatial learning and memory were impaired in DIO rats compared to those of Ctr. NR2B expression was increased, while BDNF expression and CaMKII and CREB activation were decreased in DG of DIO rats. Extracellular concentration of Glu was increased in Ctr on the 3rd and 4th days of the MWM test, but significant further increment was observed in DIO rats. Microinjection of an NMDA antagonist (MK-801) into the DG reversed spatial learning and memory impairment. Such effects were accompanied by greater BDNF expression and CaMKII/CREB activation in the DG of DIO rats. In conclusion, the enhancement of Glu-NMDA receptor transmission in the hippocampal DG contributes to the impairment of spatial learning and memory in DIO rats, maybe via the modulation of CaMKII-CREB-BDNF signaling pathway.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multimodal cortical neuronal cell type classification.","authors":"Xiaoyi Mao, Jochen F Staiger","doi":"10.1007/s00424-024-02923-2","DOIUrl":"10.1007/s00424-024-02923-2","url":null,"abstract":"<p><p>Since more than a century, neuroscientists have distinguished excitatory (glutamatergic) neurons with long-distance projections from inhibitory (GABAergic) neurons with local projections and established layer-dependent schemes for the ~ 80% excitatory (principal) cells as well as the ~ 20% inhibitory neurons. Whereas, in the early days, mainly morphological criteria were used to define cell types, later supplemented by electrophysiological and neurochemical properties, nowadays. single-cell transcriptomics is the method of choice for cell type classification. Bringing recent insight together, we conclude that despite all established layer- and area-dependent differences, there is a set of reliably identifiable cortical cell types that were named (among others) intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) for the excitatory cells, which altogether comprise ~ 56 transcriptomic cell types (t-types). By the same means, inhibitory neurons were subdivided into parvalbumin (PV), somatostatin (SST), vasoactive intestinal polypeptide (VIP), and \"other (i.e. Lamp5/Sncg)\" subpopulations, which altogether comprise ~ 60 t-types. The coming years will show which t-types actually translate into \"real\" cell types that show a common set of multimodal features, including not only transcriptome but also physiology and morphology as well as connectivity and ultimately function. Only with the better knowledge of clear-cut cell types and experimental access to them, we will be able to reveal their specific functions, a task which turned out to be difficult in a part of the brain being so much specialized for cognition as the cerebral cortex.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hoda M Moghazy, Nesreen G Abdelhaliem, Sherine Ahmed Mohammed, Asmaa Hassan, Amany Abdelrahman
{"title":"Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model.","authors":"Hoda M Moghazy, Nesreen G Abdelhaliem, Sherine Ahmed Mohammed, Asmaa Hassan, Amany Abdelrahman","doi":"10.1007/s00424-024-02933-0","DOIUrl":"10.1007/s00424-024-02933-0","url":null,"abstract":"<p><p>The American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10 weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200 μg/kg/day sc) or liraglutide (0.6 mg/kg/day sc) for 6 weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kasper B Assersen, Boye L Jensen, Camilla Enggaard, Paul M Vanhoutte, Pernille B L Hansen
{"title":"Correction to: Histamine H2‑receptor antagonism improves conduit artery endothelial function and reduces plasma aldosterone level without lowering arterial blood pressure in angiotensin II-hypertensive mice.","authors":"Kasper B Assersen, Boye L Jensen, Camilla Enggaard, Paul M Vanhoutte, Pernille B L Hansen","doi":"10.1007/s00424-024-02955-8","DOIUrl":"10.1007/s00424-024-02955-8","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catharina J Küng, Arezoo Daryadel, Rocio Fuente, Betül Haykir, Martin Hrabĕ de Angelis, Nati Hernando, Isabel Rubio-Aliaga, Carsten A Wagner
{"title":"A novel mouse model for familial hypocalciuric hypercalcemia (FHH1) reveals PTH-dependent and independent CaSR defects.","authors":"Catharina J Küng, Arezoo Daryadel, Rocio Fuente, Betül Haykir, Martin Hrabĕ de Angelis, Nati Hernando, Isabel Rubio-Aliaga, Carsten A Wagner","doi":"10.1007/s00424-024-02927-y","DOIUrl":"10.1007/s00424-024-02927-y","url":null,"abstract":"<p><p>The Calcium-sensing receptor (CaSR) senses extracellular calcium, regulates parathyroid hormone (PTH) secretion, and has additional functions in various organs related to systemic and local calcium and mineral homeostasis. Familial hypocalciuric hypercalcemia type I (FHH1) is caused by heterozygous loss-of-function mutations in the CaSR gene, and is characterized by the combination of hypercalcemia, hypocalciuria, normal to elevated PTH, and facultatively hypermagnesemia and mild bone mineralization defects. To date, only heterozygous Casr null mice have been available as model for FHH1. Here we present a novel mouse FHH1 model identified in a large ENU-screen that carries an c.2579 T > A (p.Ile859Asn) variant in the Casr gene (Casr<sup>BCH002</sup> mice). In order to dissect direct effects of the genetic variant from PTH-dependent effects, we crossed Casr<sup>BCH002</sup> mice with PTH deficient mice. Heterozygous Casr<sup>BCH002</sup> mice were fertile, had normal growth and body weight, were hypercalcemic and hypermagnesemic with inappropriately normal PTH levels and urinary calcium excretion replicating some features of FHH1. Hypercalcemia and hypermagnesemia were independent from PTH and correlated with higher expression of claudin 16 and 19 in kidneys. Likewise, reduced expression of the renal TRPM6 channel in Casr<sup>BCH002</sup> mice was not dependent on PTH. In bone, mutations in Casr rescued the bone phenotype observed in Pth null mice by increasing osteoclast numbers and improving the columnar pattern of chondrocytes in the growth zone. In summary, Casr<sup>BCH002</sup> mice represent a new model to study FHH1 and our results indicate that only a part of the phenotype is driven by PTH.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hin Heng Lo, Tawan Munkongcharoen, Rosa M Muijen, Ritika Gurung, Anjali G Umredkar, Mark D Baker
{"title":"Application of near infra-red laser light increases current threshold in optic nerve consistent with increased Na<sup>+</sup>-dependent transport.","authors":"Hin Heng Lo, Tawan Munkongcharoen, Rosa M Muijen, Ritika Gurung, Anjali G Umredkar, Mark D Baker","doi":"10.1007/s00424-024-02932-1","DOIUrl":"10.1007/s00424-024-02932-1","url":null,"abstract":"<p><p>Increases in the current threshold occur in optic nerve axons with the application of infra-red laser light, whose mechanism is only partly understood. In isolated rat optic nerve, laser light was applied near the site of electrical stimulation, via a flexible fibre optic. Paired applications of light produced increases in threshold that were reduced on the second application, the response recovering with increasing delays, with a time constant of 24 s. 3-min duration single applications of laser light gave rise to a rapid increase in threshold followed by a fade, whose time-constant was between 40 and 50 s. After-effects were sometimes apparent following the light application, where the resting threshold was reduced. The increase in threshold was partially blocked by 38.6 mM Li<sup>+</sup> in combination with 5 <math><mi>μ</mi></math> M bumetanide, a manoeuvre increasing refractoriness and consistent with axonal depolarization. Assessing the effect of laser light on the nerve input resistance ruled out a previously suggested fall in myelin resistance as contributing to threshold changes. These data appear consistent with an axonal membrane potential that partly relies on temperature-dependent electroneutral Na<sup>+</sup> influx, and where fade in the response to the laser may be caused by a gradually diminishing Na<sup>+</sup> pump-induced hyperpolarization, in response to falling intracellular [Na<sup>+</sup>].</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Angiotensin receptors and α1B-adrenergic receptors regulate native IK(ACh) and phosphorylation-deficient GIRK4 (S418A) channels through different PKC isoforms.","authors":"Leonie Inderwiedenstraße, Marie‐Cécile Kienitz","doi":"10.1007/s00424-024-02966-5","DOIUrl":"https://doi.org/10.1007/s00424-024-02966-5","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140663041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}