title: Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat.
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 pτ 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 normotensive Wistar rats, numbers of Aβ- and pτ-positive neurons in the cerebral cortex progressively increased with age until 18 months in the SHR-SR rats, as did the numbers of ionized calcium-binding 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 pτ-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 pτ.
  
  
  CONCLUSIONS
  The present study suggests that accumulation of cellular Aβ and pτ 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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Violeta
authors.initials: V
authors.lastname: Lukic
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kozuki
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wada
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: toko11@cc.okayama-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000077333:Telmisartan; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C100745:Aif1 protein, rat; D016229:Amyloid beta-Peptides; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D000077333:Telmisartan
keywords: Alzheimer's disease; inflammation; spontaneously hypertensive rat; telmisartan