Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat

Tomoko Kurata, Violeta Lukic, Miki Kozuki, Daisuke Wada, Kazunori Miyazaki, Nobutoshi Morimoto, Yasuyuki Ohta, Kentaro Deguchi, Yoshio Ikeda, Tatsushi Kamiya, Koji Abe

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Abstract

Background: In addition to reducing the level of blood pressure (BP), telmisartan was expected to show the long-term neuroprotective effects preventing accumulation of cellular amyloid beta peptide (Aβ ) and phosphorylated tau (pτ ) by ameliorating neuroinflammation. Methods: We examined effects of telmisartan on cellular Aβ and pt with inflammatory responses in the brain of a spontaneously hypertensive stroke resistant (SHR-SR) rat by giving either telmisartan at 0 (vehicle), .3 mg/kg/ day or 3 mg/kg/day, orally, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months. Compared with normotensiveWistar rats, numbers of Aβ - and pt-positive neurons in the cerebral cortex progressively increased with age until 18 months in the SHR-SR rats, as did the numbers of ionized calciumbinding adapter molecule 1 (Iba-1)-positive microglia, tumor necrosis factor alpha (TNF-α )-positive neurons, and monocyte chemotactic protein 1 (MCP-1)-positive neurons. Results: Low-dose telmisartan significantly decreased the numbers of Aβ - and pt-positive neuron as well as the numbers of TNF-α -positive neurons, Iba-1-positive microglia, and MCP-1-positive neurons at 6, 12 and 18 months. High-dose telmisartan reduced BP and showed a further reduction of cellular Aβ and pt. Conclusions: The present study suggests that accumulation of cellular Aβ and pt and the inflammatory responses were decreased via improving metabolic syndrome with low-dose telmisartan and improving both metabolic syndrome and hypertension with high-dose telmisartan.

Original languageEnglish
Pages (from-to)2580-2590
Number of pages11
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number10
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Alzheimer's disease
  • Inflammation
  • Spontaneously hypertensive rat
  • Telmisartan

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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