Pharmacology

Biography

Biography: Fleisher-Berkovich S

Abstract

The pathology of Alzheimer's disease (AD) is associated with brain inflammation, which includes the involvement of glial cells e.g., microglia and astrocytes. Microglial activation by amyloid β (Aβ) (component of AD plaque) results in the production of various inflammatory mediators, oxidative radicals, and neurotoxic cytokines, which contribute to synaptic impairment and neuronal damage. Accumulating evidence indicate that the renin-angiotensin system (RAS) may contribute to the brain inflammation associated with AD pathology. Angiotensin II (Ang II) is considered as the major RAS effector, and acts mainly via stimulation of the angiotensin type 1 receptor (AT1R). Specific inhibition of brain RAS has been suggested as a potential therapeutic strategy for AD. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and to understand the possible implications for brain inflammation and AD in vitro and in vivo. Long term exposure of BV2 microglia to telmisartan (1-5 mM) decreased by about 50% the lipopolysaccharide (LPS)-induced nitric oxide (NO), inducible NO synthase (iNOS) and tumor necrosis factor  a (TNF- a) synthesis. Telmisartan did not affect the basal synthesis of these pro-inflammatory mediators in non-stimulated BV2 cells. Cell  viability was not altered following telmisartan treatment. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and microglia/macrophages activation in the cortex and hippocampus of five familial Alzheimer’s disease (5XFAD) mouse model. Based on these results, it is suggested that telmisartan act as an anti-inflammatory and a neuroprotective agent in the brain through modulation of microglial activation and of amyloid pathology.

This research was supported by the Israel Science Foundation (grant 101/11-16).