Date Published: April 17, 2018
Publisher: Impact Journals
Author(s): Teng Jiang, Liu-Jun Xue, Yang Yang, Qing-Guang Wang, Xiao Xue, Zhou Ou, Qing Gao, Jian-Quan Shi, Liang Wu, Ying-Dong Zhang.
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.
In the process of aging, human brain displays a gradually enhanced inflammatory status called ‘inflamm-aging’ . Although this status is crucial for the brain to remove senescent cells and extrinsic pathogenic substances, recent evidence has proven that chronic neuroinflammation is detrimental for the brain and may contribute to the etiology of various aging-related neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [2-4]. This notion was supported by previous findings that anti-inflammatory therapies could halt the progression of AD and PD in animal models [5,6].
First, in this study, we showed a progressively enhanced inflammatory response in the aged brain, since the expression of inflammatory markers including IL-1β, IL-6, and TNF-α was significantly increased in SAMP8 mice brain during the aging process. These results were compatible with previous findings from our group and others that SAMP8 mice exhibited a chronic neuroinflammatory status [25,26]. Meanwhile, we demonstrated that the levels of Ang-(1-7) was significantly reduced in the aged brain, and these findings were in accordance with our previous observations in SAMP8 mice .