@article{8586419c5e1445ed93d94eb1aad2a8d1,
title = "Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior",
abstract = "Angiotensin II receptor blockers (telmisartan) prevent rodents from diet-induced obesity and improve their metabolic status. Hyperglycemia and obesity are associated with reduced cerebral blood flow and neurovascular uncoupling which may lead to behavioral deficits. We wanted to know whether a treatment with telmisartan prevents these changes in obesity. We put young mice on high-fat diet and simultaneously treated them with telmisartan. At the end of treatment, we performed laser speckle imaging and magnetic resonance imaging to assess the effect on neurovascular coupling and cerebral blood flow. Different behavioral tests were used to investigate cognitive function. Mice developed diet-induced obesity and after 16, not 8 weeks of high-fat diet, however, the response to whisker pad stimulation was about 30% lower in obese compared to lean mice. Simultaneous telmisartan treatment increased the response again by 10% compared to obese mice. Moreover, telmisartan treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented a diet-induced anxiety-like behavior. In addition to that, telmisartan affects cellular senescence and string vessel formation in obesity. We conclude, that telmisartan protects against neurovascular unit impairments in a diet-induced obesity setting and may play a role in preventing obesity related cognitive deficits in Alzheimer{\textquoteright}s disease.",
keywords = "Cerebral blood flow, neurovascular coupling, obesity, renin angiotensin system, telmisartan",
author = "Gianna Huber and Mikolaj Ogrodnik and Jan Wenzel and Ines St{\"o}lting and Lukas Huber and Olga Will and Eva Peschke and Urte Matschl and H{\"o}vener, {Jan Bernd} and Markus Schwaninger and Diana Jurk and Walter Raasch",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by research grants from the German Research Foundation to the GRK 1957 “Adipocyte-Brain Crosstalk”, University of L{\"u}beck and GRK 2154 “Materials for Brain”, University of Kiel, a grant of the German Centre for Cardiovascular Research (DZHK) and by the Cluster of Excellence PMI 1267. Acknowledgments Funding Information: We thank Sonja Binder (Institute for Experimental and Clinical Pharmacology and Toxicology, University of L{\"u}beck) for providing her expertise in animal behavior experiments, Jens Mittag (Medical Clinic 1, UKSH, L{\"u}beck) for providing the blood pressure measurement system, and Jan Sedlacik (Biomedical Engineering & Imaging Sciences, King{\textquoteright}s College London) for providing advice for MRI performance and analysis. Kiel University and the Medical Faculty are acknowledged for supporting the Molecular Imaging North Competence Center (MOIN CC) as a core facility for imaging in vivo and telmisartan was a kind gift from B{\"o}hringer Ingelheim, Germany. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by research grants from the German Research Foundation to the GRK 1957 “Adipocyte-Brain Crosstalk”, University of L{\"u}beck and GRK 2154 “Materials for Brain”, University of Kiel, a grant of the German Centre for Cardiovascular Research (DZHK) and by the Cluster of Excellence PMI 1267. Publisher Copyright: {\textcopyright} The Author(s) 2021.",
year = "2021",
month = sep,
doi = "10.1177/0271678X211003497",
language = "English (US)",
volume = "41",
pages = "2356--2369",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "9",
}