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Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.

Abstract
Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ₄₂, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.
AuthorsGuan Tao Du, Meng Hu, Zhen Lin Mei, Chao Wang, Guang Jun Liu, Mei Hu, Yan Long, Ming Xing Miao, Jia Chang Li, Hao Hong
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 124 Issue 4 Pg. 418-26 ( 2014) ISSN: 1347-8648 [Electronic] Japan
PMID24671053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Benzoates
  • Peptide Fragments
  • Receptor for Advanced Glycation End Products
  • Transcription Factor RelA
  • amyloid beta-protein (1-42)
  • Streptozocin
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse
  • Telmisartan
Topics
  • Administration, Oral
  • Amyloid Precursor Protein Secretases (metabolism)
  • Amyloid beta-Peptides (metabolism)
  • Amyloid beta-Protein Precursor (metabolism)
  • Angiotensin II Type 1 Receptor Blockers (administration & dosage, pharmacology, therapeutic use)
  • Animals
  • Aspartic Acid Endopeptidases (metabolism)
  • Benzimidazoles (administration & dosage, pharmacology, therapeutic use)
  • Benzoates (administration & dosage, pharmacology, therapeutic use)
  • Cerebral Amyloid Angiopathy (drug therapy, etiology)
  • Cerebral Cortex (metabolism)
  • Diabetes Mellitus, Experimental (complications)
  • Diabetes Mellitus, Type 1 (complications)
  • Disease Models, Animal
  • Hippocampus (metabolism)
  • Male
  • Memory Disorders (drug therapy, etiology)
  • Mice
  • Mice, Inbred ICR
  • Peptide Fragments (metabolism)
  • Receptor for Advanced Glycation End Products (metabolism)
  • Streptozocin
  • Telmisartan
  • Transcription Factor RelA (metabolism)
  • Treatment Outcome

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