Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging

NEUROBIOLOGY OF AGING

卷:100

Article

Zweig, Jonathan A.¹  Brandes, Mikah S.¹  Brumbach, Barbara H.²  Caruso, Maya¹  Wright, Kirsten M.¹  Quinn, Joseph F.^1,3  Soumyanath, Amala¹  Gray, Nora E.¹ 

[1] Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA

[2] Oregon Hlth & Sci Univ, Biostat & Design Program, Portland, OR 97201 USA

[3] VA Portland Healthcare Syst, Dept Neurol, Portland, OR USA

关键词: Aging;    Cognitive impairment;    Mitochondrial dysfunction;   

DOI  :  10.1016/j.neurobiolaging.2020.11.019

来源: Elsevier

【 摘 要 】

The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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