Sulforaphane Reduces Inflammatory Gene Expression in Microglia from Aged Mice

Abstract

Increased oxidative stress resulting from heightened microglial activation is associated with age‐related cognitive impairment, neurodegenerative disease, and response to immune stimulus. The primary compensatory mechanism for neutralizing oxidative stress is through the nuclear factor E2‐related factor 2 (Nrf2) pathway which regulates transcription of antioxidant response element (ARE) genes. Here, BV2 cells and brain CD11b+ microglial cells isolated from young adult and aged mice were used to investigate the effects of sulforaphane (SFN), a potent Nrf2‐inducing bioactive, on ARE and inflammatory gene expression associated with increased age. We hypothesized that SFN would upregulate ARE genes in primary microglial cells and that this would attenuate elevated proinflammatory cytokine expression in microglia from aged mice. In support of our hypothesis, SFN upregulated antioxidant genes NAD(P)H dehydrogenase, quinone 1 (NQO1), heme oxygenase‐1 (HMOX1), and the modulatory subunit of glutamate‐cysteine ligase, modifier subunit (GCLM) in BV2 cells and primary microglia. Primary microglia from aged mice had higher expression of interleukin (IL‐)1β, IL‐6, and inducible nitric oxide synthase (iNOS) than adult controls, and SFN reduced IL‐1β and iNOS in microglia from aged mice. Taken together these data indicate that SFN is a potential therapeutic supplement that may be beneficial for reducing microglia‐mediated neuroinflammation and oxidative stress associated with aging.Supported by NIH RO1AG16710