Change of Nrf2 expression in rat hippocampus in a model of chronic cerebral hypoperfusion

Abstract

Chronic cerebral hypoperfusion (CCH) is common in vascular dementia and Alzheimer's disease. CCH-related oxidative damage plays a significant role in the development of cognitive impairment. Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediates activation of the antioxidant responsive element (ARE)-related gene expression, which is crucial to the endogenous antioxidative system. In this case, we used permanent bilateral occlusion of common carotid arteries (2VO) to mimic CCH. The expression of Nrf2 in different regions of the hippocampus as well as the ability of nuclear Nrf2 and ARE binding have been examined. A phenomenon has been observed that the DNA binding activities were down-regulated. Interestingly, the expression of Nrf2 rose significantly in most regions of rat hippocampus within three weeks after the 2VO surgery. The mismatch might attribute to Nrf2 dysfunction and compensatory synthesis. A conclusion can be drawn that Nrf2 dysfunction is an important factor as a cause of CCH-induced oxidative damage and Nrf2 can be treated as a promising target to alleviate oxidative damage, even cognitive impairment caused by CCH.

KEYWORDS: :

• chronic cerebral hypoperfusion
• hippocampus
• Nuclear factor-erythroid 2-related factor-2
• oxidative stress