Selenium supplementation enhanced the expression of selenoproteins in hippocampus and played a neuroprotective role in LPS-induced neuroinflammation

Abstract

Selenium (Se) is obtained from organic and inorganic selenium food content, which mainly depends on the regional soil selenium content. Selenium deficiency and decreased selenoprotein functions have been shown to associate with the progression of cognitive decline and neurodegenerations including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Selenoproteins are well recognized for their anti-oxidative activities. Given the high oxygen consumption, mammalian brains preferent@ially supplied with Se.Here, we propose a beneficiary role for dietary supplementation of sodium selenite (300 ng per gram of body weight) in ameliorating neuroinflammation induced by bilateral intracerebroventricular injection of 1 μL LPS (1 μg/μL), evidenced by the significantly reduced oxidative stress, downregulated pro-inflammatory cytokines expression, improved integrity of blood-brain barrier, as well as suppressed glial activation and shifted microglial MI/M2 polarization in Se-sup mouse brain. Se intake also reduced neural cell death and significantly improved the cognition in Se-sup mice following LPS challenge. The neuroprotective role for supplementary Se is likely to be ascribed to the overall elevated expression of selenoproteins, especially Selenoprotein P (SELENOP) and Glutathione peroxidase 4 (GPX4), ranking on top of the change in selenoprotein expression hierarchy. The regional hierarchy of Se induced elevation of SELENOP expression was further characterized. The SELENOP expression in the mediodorsal thalamic nucleus, dendric gyrus (DG) and cornu ammonis 3 (CA3) of hippocampus and lateral habenular nucleus was highly sensitive to dietary Se intake.