Telmisartan Treatment Ameliorates Memory Deficits in Streptozotocin-Induced Diabetic Mice via Attenuating Cerebral Amyloidosis

Abstract

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 Ab 42 , APP, BACE1, RAGE, and NF-kB 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.

Low-Molecular-Weight NGF Mimetic Corrects the Cognitive Deficit and Depression-like Behavior in Experimental Diabetes

“…These results agree with the data on cognitive impairment in STZ-induced diabetes [43]. Intraperitoneal administration of GK-2 caused a statistically significant increase in the number of animals that found the platform on days 2, 4, and 8 of training compared to the animals in the active control group.…”

“…We reproduced the known model of diabetes mellitus with specific behavioral signs [25, 43] and described for the first time the ability of GK-2, the low-molecular-weight mimetic of the nerve growth factor, to eliminate these behavioral disorders. The main role in the development of a deficiency of NGF in diabetes is known to be its reduced formation from the proNGF precursor as a result of hyperglycemia-induced oxidative stress [44, 45], which suppresses protease activity and shifts the proNGF/NGF ratio towards the precursor prevalence that promotes apoptosis of insulin-secreting cells, contrary to mature NGF, exerting an antiapoptotic effect ( Fig.…”

Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice

“…Mice were fasted for 12 h and then injected with STZ (dissolved in sodium citrate buffer [pH = 4.5]) by single intravenous administration at 150 mg/kg [22] to induce hyperglycemic state as diabetes mice model. Glucose-oxidized method and enzymelinked immunosorbent assay were used to measure the fasting blood glucose (FBG) and serum insulin levels, respectively.…”

Telmisartan — skuteczny lek w zapobieganiu i leczeniu chorób układu sercowo-naczyniowego

“…Wykazano także pewne korzystne właściwości w odniesieniu do ośrodkowego układu nerwowego. Udowodniono, że stosowanie telmisartanu zmniejsza w nim stres oksydacyjny, redukuje akumulację amyloidu i niekorzystną fosforylację niektórych białek [37,38].…”