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Datasaet for: Acute Effects of Slow-Paced Breathing on Measures of HRV in Hospitalized Patients With Bilateral COVID-19 Pneumonia: A Secondary Analysis of a Randomized Clinical Trial
(Universität Ulm, 2024-10-29) Jarczok, Marc N.; Grüner, Beate; Gündel, Harald
This study evaluated the feasibility and effectiveness of slow-paced breathing (SPB) with prolonged exhalation in hospitalized COVID-19 pneumonia patients. Conducted as a randomized controlled trial, it demonstrated that SPB significantly increased heart rate variability (HRV) measures during SPB even in severely ill patients with reduced baseline HRV. SPB was found to be a safe, self-performed intervention that may help boost autonomic function in critically ill patients, suggesting its potential therapeutic value beyond COVID-19.
Datenset: RaSDA – 15-Jahres Ergebnisse der multizentrischen, randomisierten Studie zahnärztlich-prothetischer Therapieformen der verkürzten Zahnreihe
(Universität Ulm, 2024-10-18) Zeh, Luisa; Rudolph, Heike
Die Daten umfassen die 15-Jahres Ergebnisse der multizentrischen, randomisierten Studie zahnärztlich-prothetischer Therapieformen der verkürzten Zahnreihe (RaSDA - Randomized Shortened Dental Arch Study). Diese Studie verglich die Wirkungen und Nebenwirkungen von zwei Therapieoptionen. Die Therapieoptionen waren der Molarenersatz durch herausnehmbare Prothesen oder der nicht-Ersatz der Molaren durch den Erhalt oder die prothetische Rekonstruktion einer verkürzten Zahnreihe. In die RaSDA-Studie wurden 215 Patienten eingeschlossen.
Erratum zu: Skript zur Datenauswertung mit der Statistik-Software R, entwickelt und verwendet im Rahmen der Dissertation „Intraoperative Bestimmung des Blutvolumens von herzchirurgischen Patienten zur Steuerung der Antikoagulation: Untersuchung neuer Ansätze und Methodenvergleich“
(Universität Ulm, 2024-05-28) Nannen, Gerrit
Das hier veröffentlichte Skript wurde im Rahmen der Datenauswertung und Grafikerzeugung mit dem Statistikprogramm R im Rahmen der Dissertation "Intraoperative Bestimmung des Blutplasmavolumen von herzchirurgischen Patienten zur Steuerung der Antikoagulation: Untersuchung neuer Ansätze und Methodenvergleich" von Gerrit Nannen geschrieben und eingesetzt. Es berechnet aus fotometrischen Signalen das Blutplasmavolumen nach einer Dilution mit einem bekanntem Volumen. Außerdem erfolgt die grafische Darstellung, welche die Ergebnisse dieser Berechnung in Abhängigkeit vom jeweils genutzten fotometrischen Verfahren darstellt. Zusätzlich finden statistische Berechnungen zum Vergleich mit Idealwerten statt, um die Verfahren zu vergleichen.
Loss-of-function (LOF)/gain-of-function (GOF) polymorphisms of the ATP sensitive P2X7 influence sepsis, septic shock, pneumonia, and survival
(Universität Ulm, 2024-04) Schneider, Marion; Guggemos, Johanna; Skarratt, Kristy; Fuller, Stephen; Mayer, Benjamin
Introduction: Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Methods: Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. Results: The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis Discussion: The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.
Supplemental Data for the publication "Classification of Congenital Leptin Deficiency" (jc.2024-00117)
(Universität Ulm, 2024-04-08) Von Schnurbein, Julia; Zorn, Stefanie; Nunziata, Adriana; Brandt, Stephanie; Moepps, Barbara; Funcke, Jan-Bernd; Hussain, Khalid; Farooqi, I Sadaf; Fischer-Posovszky, Pamela; Wabitsch, Martin
Purpose Bi-allelic pathogenic leptin gene variants cause severe early onset obesity usually associated with low or undetectable circulating leptin levels. Recently, variants have been described resulting in secreted mutant forms of the hormone leptin with either biologically inactive or antagonistic properties. Methods We conducted a systematic literature research supplemented by unpublished data from patients at our center as well as new in vitro analyses to provide a systematic classification of congenital leptin deficiency based on the molecular and functional characteristics of the underlying leptin variants and investigated the correlation of disease subtype with severity of the clinical phenotype. Results A total of 28 distinct homozygous leptin variants were identified in 148 patients. The identified variants can be divided into three different subtypes of congenital leptin deficiency: classical hormone deficiency (21 variants in 128 patients), biologically inactive hormone (3 variants in 12 patients) and antagonistic hormone (3 variants in 7 patients). Only 1 variant (n=1 patient) remained unclassified. Patients with biological inactive leptin have a higher percentage of 95th BMI percentile (%BMIp95) compared to patients with classical hormone deficiency. While patients with both classical hormone deficiency and biological inactive hormone can be treated with the same starting dose of metreleptin, patients with antagonistic hormone need a variant-tailored treatment approach to overcome the antagonistic properties of the variant leptin. Main conclusions Categorization of leptin variants based on molecular and functional characteristics helps to determine the most adequate approach to treatment of patients with congenital leptin deficiency.
Improved conversion of creatine kinase MB (CK-MB) activity into mass data by generalized additive modeling
(Universität Ulm, 2023-11-24) Hönicka, Markus; Vokshi, Arbresha; Zhou, Shaoxia; Liebold, Andreas; Mayer, Benjamin
Creatine kinase isoenzyme CK-MB is used to monitor myocardial damage. We investigated the feasibility of an interconversion of CK-MB mass and activity data to simplify multicenter trials. We modeled CK-MB data with ordinary least squares regression and with generalized additive models (GAMs) which permit the inclusion of covariates. An optimized GAM predicted CK-MB masses from activities, sex, and sampling time with an Rsquare of 0.981. Interconversion of CK-MB masses and activities by GAMs created from representative patient cohorts may help to include study centers with incompatible data into multicenter trials.
SOD2ako mouse displays a psychotic moment.
(Universität Ulm, 2023-10-25) Tsesmelis, Konstantinos
Representative video of a SOD2ako mouse displaying a psychotic moment. Left: SOD2ako mouse, Right: WT mouse.
Intraoperative Bestimmung des Blutplasmavolumen von herzchirurgischen Patienten zur Steuerung der Antikoagulation: Untersuchung neuer Ansätze und Methodenvergleich
(Universität Ulm, 2023-10-24) Nannen, Gerrit
Das hier veröffentlichte Skript wurde im Rahmen der Datenauswertung und Grafikerzeugung mit dem Statistikprogramm R im Rahmen der Dissertation "Intraoperative Bestimmung des Blutplasmavolumen von herzchirurgischen Patienten zur Steuerung der Antikoagulation: Untersuchung neuer Ansätze und Methodenvergleich" von Gerrit Nannen geschrieben und eingesetzt. Es berechnet aus fotometrischen Signalen das Blutplasmavolumen nach einer Dilution mit einem bekanntem Volumen. Außerdem erfolgt die grafische Darstellung, welche die Ergebnisse dieser Berechnung in Abhängigkeit vom jeweils genutzten fotometrischen Verfahren darstellt. Zusätzlich finden statistische Berechnungen zum Vergleich mit Idealwerten statt, um die Verfahren zu vergleichen.
Research data on: Ventilation and perfusion assessment by functional MRI with non-contrast-enhanced 2D ultra-short echo time (UTE)
(Universität Ulm, 2023) Yang, Bingjie
Respiratory phase images were reconstructed applying an image-based self-gating technique. Multi-cardiac phase images were reconstructed applying k0-based self-gating technique. The images of segmented lung over the respiratory cycle after segmentation and registration to the end-expiratory reference phase had been adjusted for lung parenchyma visualization.
Extraktionsalgorithmus: Intensivstation-Verlegungsberichte
(Universität Ulm, 2023-03-08) Hawe, Johann; Krefting, Johannes
Der Algorithmus wurde entwickelt, um Informationen aus Verlegungsberichten von Intensivstationen (ICU) zu extrahieren und in einer Excel-Tabelle zusammenzuführen. Der Prozess des manuellen Auslesens wäre aufgrund der großen Anzahl von Patienten mit enormem zeitlichem Aufwand und möglichen Fehlern verbunden. Daher wurde ein Skript in R-Studio erstellt, das die Patientendaten extrahiert und in generierte Excel-Tabellen eingefügt. Aus jedem zur Verfügung stehenden Verlegungsbericht können die Informationen ausgelesen und in einer Tabelle mit einem eindeutigen Primärschlüssel zusammengeführt werden. Die extrahierten Daten werden in Stammdaten (Größe, Alter, Gewicht), Operationsbezogene Daten, Klinischer Verlauf und Verlegungskriterien unterteilt, die durch eine Suchfunktion abgerufen und einer anonymisierten Patienten-ID zugeordnet werden können.
Datenextraktionsalgorithmus: EKZ-Parameter
(Universität Ulm, 2023-03-08) Krefting, Johannes; Sagawa, Mario
Es wurde ein Python-Algorithmus entwickelt, um die Parameter von Patienten während der extrakorporalen Zirkulation (EKZ) bei Operationen zu analysieren. Die Parameter werden alle 20 Sekunden von der Herz-Lungen-Maschine (HLM) erfasst und ergeben bei einer Operation von 3 bis 10 Stunden eine enorme Datenfülle. Um diese Daten sinnvoll auswerten zu können, werden die Parameter in vordefinierte Wertbereiche eingeteilt. Dazu wurden jeweils sechs Wertintervalle mit gleichen Abständen der Intervallgrenzen definiert, wobei Ausnahmen bei der Blutflussrate der HLM und dem pO2 gemacht wurden. Der Algorithmus wurde in Python implementiert. Die Excel-Tabellen der EKZ-Parameter und der Sollflüsse wurden eingelesen und einer Datenreinigung unterzogen. Die erhaltenen Werte wurden auf ihre Normalverteilung mittels Shapiro-Wilk-Test und D’Agostino K2-Test überprüft und in einer exportierfähigen Tabelle festgehalten.
Acute effects of single vs. combinatory inhaled β2-agonists Salbutamol and Formoterol on time trial performance, lung function, metabolic and endocrine variables
(Universität Ulm, 2023-02-14) Bizjak, Daniel Alexander; Dreyhaupt, Jens; Steinacker, Jürgen Michael; Parr, Maria Kristina
Background: High prevalence rates of β2-agonists amongst athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of β2-agonists and its underlying molecular basis are scarce. Methods: To investigate single vs. combinatory effects of the nonprohibited short-acting β2-agonists salbutamol (SAL) and long-acting formoterol (FOR), 24 competitive endurance athletes (12f/12m) participated in a double-blinded balanced 4-way block cross-over trial to evaluate the potential performance-enhancement of SAL, FOR, and SAL+FOR compared to placebo (PLA). Measurements included skeletal muscle gene and protein expression of nuclear NR4A receptors, endocrine regulation, urinary and serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing as well as the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected Pre-, Post-, 3h Post-, and 24h Post TT. Results: Mean power output during TT was not different between study arms. Treatment effects regarding lung function, echocardiographic and metabolic variables were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Muscle and microarray analysis did not show any treatment effect on NR4A protein and NR4A1/NR4A3 gene expression, whereas a whole group treatment effect was calculated for NR4A2 and further target genes in energy metabolism with strongest effect by SAL+FOR. Noradrenaline, adrenaline, insulin-like growth factor, and transforming growth factor-β concentrations in blood were not affected by treatment or sex, whereas follicle-stimulating hormone (3h Post-Post TT), luteinizing hormone (3h Post-Pre TT), and insulin (Post-Pre TT) concentrations showed a treatment effect at different time points. Conclusion: We did not find an endurance performance-enhancing effect for SAL, FOR, or SAL+FOR within the permitted dosages compared to PLA. An acute effect on lung and cardiac function as well as endocrine and metabolic variables was observed without clinically relevant side effects and presumably without impact on endurance performance in healthy participants. However, the impact of chronically applied β2-agonists on performance in healthy athletes and sex-specific thresholds for daily β2-agonists’ doses have still to be determined.
Dataset: Bounded rational decision-making models suggest capacity-limited concurrent motor planning in human posterior parietal and frontal cortex
(Universität Ulm, 2022-09-26) Schach, Sonja
Data from the fMRI study "Bounded rational decision-making models suggest capacity-limited concurrent motor planning in human posterior parietal and frontal cortex"
A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using slow-paced breathing technique
(Universität Ulm, 2022-09-20) Balint, Elisabeth; Grüner, Beate; Jarczok, Marc
Purpose: A characteristic problem occuring in COVID-19 is excessive elevations of pro-inflammatory cytokines (e.g. IL-6 and CRP) which are associated with worse clinical outcomes. Stimulation of the vagally-mediated cholinergic anti-inflammatory reflex by slow paced breathing with prolonged exhalation may present a clinically relevant way to reduce circulating IL-6. These data belong to the single-center randomized controlled clinical trial manuscript entitled: "A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique" https://www.frontiersin.org/articles/10.3389/fimmu.2022.928979/abstract Trial registration: German register of clinical trials (ID: DRKS00023971) https://www.drks.de, Universal Trial Number (UTN) U1111-1263-8658; Keywords: Cholinergic anti-inflammatory reflex, slow-paced breathing, vagus nerve stimulation, acute viral infection, moderate COVID-19 pneumonia, dose-response relationship, IL-6, CRP, TNF-alpha, Leukocytes CC BY-NC 4.0 International
Der Einfluss der Parkinson-Syndrome auf die Netzhaut - eine Analyse mittels Optischer Kohärenztomographie
(Universität Ulm, 2022-08-24) Tritarelli, Patricia
Die retinalen Schichten mittels optischer Kohärenztomographie (OCT) zu untersuchen ist eine zunehmend angewendete Methode bei neurodegenerativen Erkrankungen. Grundlegend dabei ist, dass an der Retina als Teil des ZNS strukturelle Veränderungen erkennbar sind, die pathologische Prozesse im Gehirn widerspiegeln. Die vorliegende Studie zielt auf den möglichen Unterschied der retinalen Veränderungen von drei verschiedenen neurodegenerativen Parkinson-Entitäten gegenüber von gesunden Kontrollpersonen (HC) ab. Bei den Patienten handelt es sich um Personen, welche an der Parkinson-Krankheit (Parkinson´s disease = PD), der Multisystematrophie (MSA) oder der Progressiven Supranukleären Blickparese (PSP) leiden. Zentral dabei ist der Zusammenhang zwischen den Untersuchungen mittels optischer Kohärenztomographie sowie der potentielle Einfluss von Alter, Geschlecht, motorischem Anteil des Unified Parkinson´s Disease Rating Score (UPDRS) und dem Hoehn & Yahr Score. Eine deskriptive Statistik bezüglich Alter, Geschlecht, Erkrankungsdauer, nicht motorischen Symptomen gemäß dem Non motor Symptom Fragebogen, dem III Teil des UPDRS und dem Hoehn & Yahr Score wurde neben der statistischen Analyse erstellt. Dabei erfolgte eine zweigeteilte Varianzanalyse und eine Kruskal-Wallis-Test Analyse. Insgesamt nahmen 46 Patienten (29 PD, 9 MSA, 8 PSP) und 21 HC an der Studie teil. Die Makula lutea wurde in zwei Abschnitte unterteilt: periphere parafoveale und zentrale foveale Anteile. Es erfolgte zudem eine retinale Einzelschichtanalyse. Herausragend war die Erkenntnis über die äußerste retinale, und somit über die Nervenfaserschicht, welche in einigen Subanalysen signifikant ausgedehnter bei Parkinson-Syndrom Patienten war. Die äußere plexiforme Schicht (OPL) und die retinale Nervenfaserschicht (RNFL) waren innerhalb der Gruppe der erkrankten Patienten signifikant dünner. Signifikant verdickt war außerdem die RNFL bei MSA und verdünnt die OPL bei PD. Die anfängliche eigens erstellte Hypothese, die auf vorherigen Studien basiert, dass parafoveale Anteile der Makula lutea stärker verdünnt seien als peripher gelegene Abschnitte der Retina, konnte nicht untermauert werden. Es wurde keine signifikante Verdünnung der gesamten retinalen Schichtdicke, der Ganglienzellschicht zusammen mit der inneren plexiformen Schicht sowie der ONL bei Parkinson-Syndrom Patienten gefunden. Allerdings konnte eine inverse Korrelation zwischen UPDRS III und einzelnen OPL-Unterabschnitten gezeigt werden. Mit einer höheren Anzahl an Studienteilnehmern sowie einem longitudinalen Studienmodell könnte ein Mehrwert an prädiktiven Markern zur Früherkennung der Parkinson-Syndrome mittels OCT gewonnen werden.
A novel pulsatile blood pump design for cardiothoracic surgery - proof-of-concept in a mock circulation
(Universität Ulm, 2022-05-06) Weber, Elena; Liebold, Andreas; Hönicka, Markus
Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. We investigated the properties of a novel positive displacement blood pump in a mock circulation containing an aortic model with a human-like geometry and compliance as a pseudo patient. Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mmHg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mmHg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F=40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mmHg and F=40 bpm. At F=40 bpm, PP was 58.7 mmHg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications will help to establish this concept for adult pulsatile perfusion.
Psychometric Scoring of translated Social Inclusion Scale
(Universität Ulm, 2022-01-05) Charles, Ashleigh; Puschner, Bernd
As part of the UPSIDES RCT study, the "Social Inclusion Scale" (also "Social Inclusion Measure", by Secker J., Hacking S., Kent L., Shenton J., Spandler H.) was to be measured at several international study centres. To avoid distortion of the results due to language barrier, the scale was translated and subsequently psychometrically validated. The dataset contains the results of the psychometric measurements.
Preservation of adrenoceptor and endothelin receptor mediated vasoconstriction after cold storage of explanted blood vessels for ex-vivo analyses
(Universität Ulm, 2022-01-03) Hoenicka, Markus; Sabau, Marius; Liebold, Andreas
Purpose: Cold storage of blood vessels is a concern in bypass surgery and in ex vivo pharmacological experiments. We compared adrenoceptor and endothelin receptor-mediated vasoconstriction as well as endothelium-dependent vasodilation before and after 20 h storage in commercial and custom-made vessel storage solutions. Methods: Saphenous veins harvested during coronary artery bypass surgery were analyzed by isometric force measurements in organ baths before and after cold storage for 20 h in HEPES-supplemented Dulbecco's modified Eagle's medium (HDMEM), HEPES-supplemented Krebs-Henseleit solution (HKH), or TiProtec solution. Contractile responses to potassium chloride (KCl), norepinephrine (NE), and endothelin-1 (ET-1) as well as vasodilator responses to acetylcholine (ACh) were evaluated. Results: Storage in HDMEM diminished KCl induced contractile forces to 71% (p=0.002) and NE induced contractions to 80% (p=0.037) with no significant changes with the other solutions. NE induced contractions normalized to KCl were not affected by storage. NE EC50 values were slightly lower (7.1E-8 vs. 7.5E-8, p=0.019) after storage in HKH with no changes after storage in the other solutions. Endothelium-dependent responses to ACh were not affected by storage. ET-1 induced contractions were attenuated after storage in HDMEM (77%, p=0.002), HKH (75%, p=0.020), and TiProtec (73%, p=0.010) with no changes in the KCl-normalized constrictions. ET-1 EC50 values were not affected by storage. Conclusion: Changes in contractility after storage likely reflect malnutrition during cold storage with no specific attenuation of adrenoceptor or endothelin-receptor mediated signal transduction. HKH or TiProtec are equally suitable cold storage solutions for preserving blood vessel function for ex-vivo measurements.
Supplementary Movies for the doctoral thesis "Mechanistic studies on transduction enhancing EF-C peptide nanofibrils and optimization for gene therapeutic applications".
(Universität Ulm, 2021-07) Schütz, Desiree
Supplementary movies associated with the doctoral thesis "Mechanistic studies on transduction enhancing EF-C peptide nanofibrils and optimization for gene therapeutic applications".
NADH fluorescence lifetime imaging microscopy reveals selective mitochondrial dysfunction in neurons overexpressing alzheimer’s disease–related proteins
(Universität Ulm, 2021-06-14) Niederschweiberer, Moritz A.; Schaefer, Patrick M.; Singh, Larry N.; Lausser, Ludwig; Bhosale, Devyani; Hesse, Raphael; Calzia, Enrico; Kestler, Hans A.; Rueck, Angelika; Wallace, Douglas C.; von Einem, Bjoern; von Arnim, Christine A. F.
Alzheimer’s disease (AD), the most prevalent form of dementia, affects globally more than 30 million people suffering from cognitive deficits and neuropsychiatric symptoms. Substantial evidence for the involvement of mitochondrial dysfunction in the development and/or progression of AD has been shown in addition to the pathological hallmarks amyloid beta (Aβ) and tau. Still, the selective vulnerability and associated selective mitochondrial dysfunction cannot even be resolved to date. We aimed at optically quantifying mitochondrial function on a single-cell level in primary hippocampal neuron models of AD, unraveling differential involvement of cell and mitochondrial populations in amyloid precursor protein (APP)-associated mitochondrial dysfunction. NADH lifetime imaging is a highly sensitive marker-free method with high spatial resolution. However, deciphering cellular bioenergetics of complex cells like primary neurons has still not succeeded yet. To achieve this, we combined highly sensitive NADH lifetime imaging with respiratory inhibitor treatment, allowing characterization of mitochondrial function down to even the subcellular level in primary neurons. Measuring NADH lifetime of the same neuron before and after respiratory treatment reveals the metabolic delta, which can be taken as a surrogate for cellular redox capacity. Correlating NADH lifetime delta with overexpression strength of Aβ-related proteins on the single-cell level, we could verify the important role of intracellular Aβ-mediated mitochondrial toxicity. Subcellularly, we could demonstrate a higher respiration in neuronal somata in general than dendrites, but a similar impairment of somatic and dendritic mitochondria in our AD models. This illustrates the power of NADH lifetime imaging in revealing mitochondrial function on a single and even subcellular level and its potential to shed light into bioenergetic alterations in neuropsychiatric diseases and beyond.

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