Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice
The etiology of Alzheimer’s disease (AD) has been intensively studied. However, little is known about the molecular alterations in early-stage and late-stage AD. Hence, we performed RNA sequencing and assessed differentially expressed genes (DEGs) in the hippocampus of 18-month and 7-month-old APP/PS1 mice. Moreover, the DEGs induced by treatment with nicotine, the nicotinic acetylcholine receptor agonist that is known to improve cognition in AD, were also analyzed in old and young APP/PS1 mice. When comparing old APP/PS1 mice with their younger littermates, we found an upregulation in genes associated with calcium overload, immune response, cancer, and synaptic function; the transcripts of 14 calcium ion channel subtypes were significantly increased in aged mice. In contrast, the downregulated genes in aged mice were associated with ribosomal components, mitochondrial respiratory chain complex, and metabolism. Through comparison with DEGs in normal aging from previous reports, we found that changes in calcium channel genes remained one of the prominent features in aged APP/PS1 mice. Nicotine treatment also induced changes in gene expression. Indeed, nicotine augmented glycerolipid metabolism, but inhibited PI3K and MAPK signaling in young mice. In contrast, nicotine affected genes associated with cell senescence and death in old mice. Our study suggests a potential network connection between calcium overload and cellular signaling, in which additional nicotinic activation might not be beneficial in late-stage AD.
KeywordsAlzheimer’s disease Transcriptome Hippocampus Nicotine Alternative splicing Calcium overload
This work was supported by National Nature Science Foundation of China grants (numbers 81171197 & 81220108010) to G-J C. G-J Chen and Z Yan designed research; J Yang performed research; Y Long, D-M Xu, B-L Zhu, X-J Deng and F Sun provided assistance; J Yang analyzed data; G-J Chen and J Yang wrote the paper.
This work was supported by National Natural Science Foundation of China (NSFC) grants (numbers 81171197 & 81220108010) to G-J Chen.
Compliance with Ethical Standards
All protocols were approved by the Commission of Chongqing Medical University for ethics of experiments on animals and were in accordance with international standards.
Conflict of Interest
The authors declare that they have no conflict of interest.
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