Academic Journal
Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication
| العنوان: | Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication |
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| المؤلفون: | Jacopo Agrimi, Danilo Menicucci, Jia-Hua Qu, Marco Laurino, Chelsea D. Mackey, Laila Hasnain, Yelena S. Tarasova, Kirill V. Tarasov, Ross A. McDevitt, Donald B. Hoover, Angelo Gemignani, Nazareno Paolocci, Edward G. Lakatta |
| المساهمون: | Agrimi, Jacopo, Menicucci, Danilo, Qu, Jia-Hua, Laurino, Marco, Mackey, Chelsea D., Hasnain, Laila, Tarasova, Yelena S., Tarasov, Kirill V., Mcdevitt, Ross A., Hoover, Donald B., Gemignani, Angelo, Paolocci, Nazareno, Lakatta, Edward G. |
| سنة النشر: | 2023 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | Granger causality, adenylyl cyclase type 8, electroencephalogram gamma rhythm, heart-brain communication, locomotor activity, stress |
| الوصف: | Background: The central nervous system's influence on cardiac function is well described; however, direct evidence for signaling from heart to brain remains sparse. Mice with cardiac-selective overexpression of adenylyl cyclase type 8 (TGAC8) display elevated heart rate/contractility and altered neuroautonomic surveillance. Objectives: In this study the authors tested whether elevated adenylyl cyclase type 8-dependent signaling at the cardiac cell level affects brain activity and behavior. Methods: A telemetry system was used to record electrocardiogram (ECG) and electroencephalogram (EEG) in TGAC8 and wild-type mice simultaneously. The Granger causality statistical approach evaluated variations in the ECG/EEG relationship. Mouse behavior was assessed via elevated plus maze, open field, light-dark box, and fear conditioning tests. Transcriptomic and proteomic analyses were performed on brain tissue lysates. Results: Behavioral testing revealed increased locomotor activity in TGAC8 that included a greater total distance traveled (+43%; P < 0.01), a higher average speed (+38%; P < 0.01), and a reduced freezing time (-45%; P < 0.01). Dual-lead telemetry recording confirmed a persistent heart rate elevation with a corresponding reduction in ECG-R-waves interval variability and revealed increased EEG-gamma activity in TGAC8 vs wild-type. Bioinformatic assessment of hippocampal tissue indicated upregulation of dopamine 5, gamma-aminobutyric acid A, and metabotropic glutamate 1/5 receptors, major players in gamma activity generation. Granger causality analyses of ECG and EEG recordings showed a marked increase in informational flow between the TGAC8 heart and brain. Conclusions: Perturbed signals arising from the heart cause changes in brain activity, altering mouse behavior. More specifically, the brain interprets augmented myocardial humoral/functional output as a "sustained exercise-like" situation and responds by activating central nervous system output controlling locomotion. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37737772; info:eu-repo/semantics/altIdentifier/wos/WOS:001129884000001; volume:9; firstpage:2219; lastpage:2235; numberofpages:17; journal:JACC. CLINICAL ELECTROPHYSIOLOGY; https://hdl.handle.net/11568/1297027; https://pubmed.ncbi.nlm.nih.gov/37737772/ |
| DOI: | 10.1016/j.jacep.2023.07.023 |
| الاتاحة: | https://hdl.handle.net/11568/1297027 https://doi.org/10.1016/j.jacep.2023.07.023 https://pubmed.ncbi.nlm.nih.gov/37737772/ |
| رقم الانضمام: | edsbas.4E0B3A6A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jacep.2023.07.023 |
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