Telmisartan prevented cognitive decline partly due to PPAR-gamma activation.

Abstract

Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-gamma. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of Abeta 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-gamma antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-gamma agonistic effect, also inhibited Abeta-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for Abeta showed the reduced Abeta deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-gamma activation, could exert a stronger effect.

• Authors: Masaki Mogi, Jian-Mei Li, Kana Tsukuda, Jun Iwanami, Li-Juan Min, Akiko Sakata, Teppei Fujita, Masaru Iwai, Masatsugu Horiuchi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 375 Issue 3 Pg. 446-9 (Oct 24 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18715543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-chloro-5-nitrobenzanilide
• Amyloid beta-Peptides
• Angiotensin II Type 1 Receptor Blockers
• Anilides
• Benzimidazoles
• Benzoates
• PPAR gamma
• Losartan
• Telmisartan

Topics

• Amyloid beta-Peptides (metabolism, toxicity)
• Angiotensin II Type 1 Receptor Blockers (administration & dosage)
• Anilides (pharmacology)
• Animals
• Benzimidazoles (administration & dosage)
• Benzoates (administration & dosage)
• Brain (drug effects, metabolism, pathology)
• Cognition Disorders (chemically induced, metabolism, pathology, prevention & control)
• Losartan (administration & dosage)
• Male
• Mice
• Mice, Inbred Strains
• PPAR gamma (agonists)
• Telmisartan