Cannabidiol (CBD) enhanced the hippocampal immune response and autophagy of APP/PS1 Alzheimer's mice uncovered by RNA-seq

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Abstract
Alzheimer’s disease (AD) is a central nervous system disease characterized by dementia, which has now become a major threat to global health. Cannabidiol (CBD) is a natural component extracted from the hemp plant and exhibits multiple mechanisms to improve the pathological process of AD in vitro and in vivo. However, its underlying molecular mechanism is still unclear. This study attempts to reveal its common mechanism through transcriptome sequence. We performed transcriptome sequence in the hippocampus of 6 month old APP/PS1 mice chronically treated with CBD for one month or 30 days. In addition, Aβ plaques were investigated by Immunohistochemistry. Autophagosomes were observed by transmission electron microscopy and the expression of autophagy related proteins was examined by Western blot. GO_BP and KEGG enriched analysis showed that the immune system response was up-regulation significantly. Both KEGG pathway analysis and GSEA analysis showed that autophagy was significantly up-regulated. Finally, the autophagy of hippocampal neurons in APP/PS1 mice treated with CBD was significantly enhanced by transmission electron microscopy. This study illustrated that CBD may improve the pathological process of AD by enhancing immune system response and autophagy pathway.