Telmisartan protects against cognitive decline via up-regulation of brain-derived neurotrophic factor/tropomyosin-related kinase B in hippocampus of hypertensive rats

SummaryBackground and purposeCognitive decline may occur as a result of hypertension, and is dependent on the function of hippocampus. Brain-derived neurotrophic factor (BDNF) mediated by angiotensin II-induced oxidative stress protects against cell death in hippocampus. Angiotensin II receptor blocker (ARB), candesartan, activates BDNF in the hippocampus. Furthermore, peroxisome proliferator-activated receptor (PPAR)-gamma activation in the brain prevents brain damage. Telmisartan, a unique ARB with PPAR-gamma stimulating activity, protects against cognitive decline partly because of PPAR-gamma activation. The aim of the present study was to determine whether telmisartan protects against cognitive decline via up-regulation of BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of hypertensive rats, partly because of PPAR-gamma activation.Methods and resultsWe divided stroke-prone spontaneously hypertensive rats (SHRSPs), as hypertensive and vascular dementia model rats, into five groups, telmisartan-treated (TLM), TLM + GW9662, a PPAR-gamma inhibitor, -treated (T + G), GW9662-treated (GW), TLM + ANA-12, a TrkB antagonist, -treated (T + A), and vehicle-treated SHRSPs (VEH). After the treatment for 28 days, systolic blood pressure did not change in all groups. However, BDNF expression in the hippocampus was significantly higher in TLM than in VEH to a greater extent than in T + G. Cognitive performance was significantly higher in TLM than in VEH to a greater extent than in T + G, and was not different between T + A, GW, and VEH.ConclusionTelmisartan protects against cognitive decline via up-regulation of BDNF/TrkB in the hippocampus of SHRSPs, partly because of PPAR-gamma activation independent of blood pressure-lowering effect.