title: 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.
authors.affiliation: Department of Pharmacy, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, China.
authors.forename: Guan Tao
authors.initials: GT
authors.lastname: Du
authors.forename: Meng
authors.initials: M
authors.lastname: Hu
authors.forename: Zhen Lin
authors.initials: ZL
authors.lastname: Mei
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Guang Jun
authors.initials: GJ
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.forename: Ming Xing
authors.initials: MX
authors.lastname: Miao
authors.forename: Jia
authors.initials: J
authors.lastname: Chang Li
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
mesh_terms: D000284:Administration, Oral; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016657:Cerebral Amyloid Angiopathy / Q000188:drug therapy* / Q000209:etiology*; D002540:Cerebral Cortex / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D013311:Streptozocin; D000077333:Telmisartan; D051996:Transcription Factor RelA / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D051996:Transcription Factor RelA; C075222:amyloid beta-protein (1-42); D013311:Streptozocin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D000077333:Telmisartan