Alzheimer Disease: Recent Updates on Apolipoprotein E and Gut Microbiome Mediation of Oxidative Stress, and Prospective Interventional Agents.

Alzheimer's disease (AD) is a current public health challenge and will remain until the development of an effective intervention. However, developing an effective treatment for the disease requires a thorough understanding of its etiology, which is currently lacking. Although several studies have shown the association between oxidative damage and AD, only a few have clarified the specific mechanisms involved. Herein, we reviewed recent preclinical and clinical studies that indicated the significance of oxidative damage in AD, as well as potential antioxidants. Although several factors regulate oxidative stress in AD, we centered our investigation on apolipoprotein E and the gut microbiome. Apolipoprotein E, particularly apolipoprotein E-ε4, can impair the structural facets of the mitochondria. This, in turn, can minimize the mitochondrial functionality and result in the progressive build-up of free radicals, eventually leading to oxidative stress. Similarly, the gut microbiome can influence oxidative stress to a significant degree via its metabolite, trimethylamine N-oxide. Given the various roles of these two factors in modulating oxidative stress, we also discuss the possible relationship between them and provide future research directions.

Serotonin receptors 2A and 1A modulate anxiety-like behavior in post-traumatic stress disordered mice.

5-hydroxytryptamine receptors 2A and 1A (5-HT2A and 5-HT1A receptors) are most closely related to anxiety-like behavior in post-traumatic stress disorder. This study was aimed at determining how 5-HT2A and 5-HT1A receptors mediate stress-induced anxiety-like behavior. C57BL/6 mice were exposed to conditioned fear stress combined with single-prolonged stress and injected with corresponding antagonists of 5-HT2A or 5-HT1A receptors or DMSO. The established mouse model was used in conjunction with open-field test, freezing behavioral test and elevated plus maze test. Protein expression levels of 5-HT2A and 5-HT1A receptors, ERK1 and ERK2, pERK1, pERK2 and c-Myc in mice hippocampus were evaluated by Western blot analysis and immunofluorescence labeling. Relative mRNA expression levels of 5-HT2A and 5-HT1A receptors, ERK1, ERK2 and c-Myc were analyzed with RT-qRCR. 5-HT2A receptor plays a significant role in anxiety-like behavior by inhibiting 5-HT1A receptor expression. Effect of 5-HT2A and 5-HT1A receptors on stress-related anxiety-like behavior was elicited via ERK1 and ERK2 phosphorylation. On the basis of our experimental results, we hypothesize interaction between 5-HT2A and 5-HT1A receptors in mouse hippocampus to mediate anxiety-like behavior via ERK pathway.