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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Amyloid Precursor Protein Secretases / metabolism
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Protein Precursor / metabolism
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Angiotensin II Type 1 Receptor Blockers / administration & dosage
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Angiotensin II Type 1 Receptor Blockers / therapeutic use*
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Animals
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Aspartic Acid Endopeptidases / metabolism
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Benzimidazoles / administration & dosage
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Benzimidazoles / pharmacology*
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Benzimidazoles / therapeutic use*
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Benzoates / administration & dosage
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Benzoates / pharmacology*
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Benzoates / therapeutic use*
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Cerebral Amyloid Angiopathy / drug therapy*
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Cerebral Amyloid Angiopathy / etiology*
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Cerebral Cortex / metabolism
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Diabetes Mellitus, Experimental / complications*
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Diabetes Mellitus, Type 1 / complications*
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Disease Models, Animal
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Hippocampus / metabolism
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Male
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Memory Disorders / drug therapy*
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Memory Disorders / etiology*
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Mice
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Mice, Inbred ICR
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Peptide Fragments / metabolism
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Receptor for Advanced Glycation End Products / metabolism
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Streptozocin
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Telmisartan
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Transcription Factor RelA / metabolism
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Treatment Outcome
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Angiotensin II Type 1 Receptor Blockers
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Benzimidazoles
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Benzoates
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Peptide Fragments
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Receptor for Advanced Glycation End Products
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Transcription Factor RelA
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amyloid beta-protein (1-42)
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Streptozocin
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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Bace1 protein, mouse
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Telmisartan