التفاصيل البيبلوغرافية
| العنوان: |
Whole-brain activation signatures of weight-lowering drugs |
| المؤلفون: |
Henrik H. Hansen, Johanna Perens, Urmas Roostalu, Jacob Lercke Skytte, Casper Gravesen Salinas, Pernille Barkholt, Ditte Dencker Thorbek, Kristoffer T.G. Rigbolt, Niels Vrang, Jacob Jelsing, Jacob Hecksher-Sørensen |
| المصدر: |
Molecular Metabolism, Vol 47, Iss , Pp 101171- (2021) |
| بيانات النشر: |
Elsevier, 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Internal medicine |
| مصطلحات موضوعية: |
Imaging, iDISCO, Light sheet fluorescence microscopy, c-Fos, Obesity, Anti-Obesity drugs, Internal medicine, RC31-1245 |
| الوصف: |
Objective: The development of effective anti-obesity therapeutics relies heavily on the ability to target specific brain homeostatic and hedonic mechanisms controlling body weight. To obtain further insight into neurocircuits recruited by anti-obesity drug treatment, the present study aimed to determine whole-brain activation signatures of six different weight-lowering drug classes. Methods: Chow-fed C57BL/6J mice (n = 8 per group) received acute treatment with lorcaserin (7 mg/kg; i.p.), rimonabant (10 mg/kg; i.p.), bromocriptine (10 mg/kg; i.p.), sibutramine (10 mg/kg; p.o.), semaglutide (0.04 mg/kg; s.c.) or setmelanotide (4 mg/kg; s.c.). Brains were sampled two hours post-dosing and whole-brain neuronal activation patterns were analysed at single-cell resolution using c-Fos immunohistochemistry and automated quantitative three-dimensional (3D) imaging. Results: The whole-brain analysis comprised 308 atlas-defined mouse brain areas. To enable fast and efficient data mining, a web-based 3D imaging data viewer was developed. All weight-lowering drugs demonstrated brain-wide responses with notable similarities in c-Fos expression signatures. Overlapping c-Fos responses were detected in discrete homeostatic and non-homeostatic feeding centres located in the dorsal vagal complex and hypothalamus with concurrent activation of several limbic structures as well as the dopaminergic system. Conclusions: Whole-brain c-Fos expression signatures of various weight-lowering drug classes point to a discrete set of brain regions and neurocircuits which could represent key neuroanatomical targets for future anti-obesity therapeutics. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2212-8778 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2212877821000119; https://doaj.org/toc/2212-8778 |
| DOI: |
10.1016/j.molmet.2021.101171 |
| URL الوصول: |
https://doaj.org/article/bd964deac5714ad4a7d015ebc7bd52eb |
| رقم الانضمام: |
edsdoj.bd964deac5714ad4a7d015ebc7bd52eb |
| قاعدة البيانات: |
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