Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer's Mice

Angiotensin receptor blockers (ARBs) have demonstrated multiple neuroprotective benefits in Alzheimer's disease (AD) models. However, their beneficial effects on memory deficits, cholinergic activity, neurogenesis and Amyloid beta (A beta) clearance reveal significant interstudy variability. The delivery route can impact not only delivery but also targeting and therapeutic efficacy of ARBs. Our previous findings on the beneficial effects of intranasally delivered losartan in the APP/PS1 model of AD prompted us to explore the influence of the delivery route by employing here the systemic administration of losartan. Consistent with our previous results with intranasal losartan, repeated intraperitoneal administration (10 mg/kg) resulted in a remarkable decrease in A beta plaques and soluble A beta 42, as well as inflammatory cytokines (IL-2, IL-6 and TNF alpha). The A beta reduction can be ascribed to its facilitated degradation by neprilysin and diminished generation by BACE1. Losartan increased neurogenesis in vivo and in vitro and improved migratory properties of astrocytes isolated from adult transgenic AD mice. In summary, this data together with our previous results suggest therapeutic features of losartan which are independent of delivery route. The improvement of cell motility of A beta-affected astrocytes by losartan deserves further in vivo investigation, which may lead to new strategies for AD treatment.

Automated summary

ARBs have shown neuroprotective benefits in AD models, with variable effects on memory deficits, cholinergic activity, neurogenesis, and A beta clearance. Systemic administration of losartan resulted in decreased A beta plaques, A beta 42, and inflammatory cytokines, while improving neurogenesis and astrocyte motility. Therapeutic features of losartan appear independent of delivery route.