Transcriptome Analysis of Pineal Glands in the Mouse Model of Alzheimer’s Disease

Abstract

The pineal gland maintains the circadian rhythm in the body by secreting the hormone melatonin. Alzheimer's disease (AD) is the most common neurodegenerative disease. Pineal gland impairment in AD is widely observed, but no study to date has analyzed the transcriptome in the pineal glands of AD. To establish resources for the study on pineal gland dysfunction in AD, we performed a transcriptome analysis of the pineal glands of AD model mice and compared them to those of wild type mice. We identified the global change of diverse protein-coding RNAs, which are implicated in the alteration in cellular transport, protein transport, protein folding, collagen expression, histone dosage, and the electron transfer system. We also discovered various dysregulated long noncoding RNAs and circular RNAs in the pineal glands of mice with AD. This study showed that the expression of diverse RNAs with important functional implications in AD was changed in the pineal gland of the AD mouse model. The analyzed data reported in this study will be an important resource for future studies to elucidate the altered physiology of the pineal gland in AD.

Identifying daily changes in circRNAs and circRNA-associated-ceRNA networks in the rat pineal gland

“…However, studies of circRNAs in the rat pineal gland have rarely been reported. Only one study reported significant differences in circRNA expression in the pineal gland of AD mice 43 . Therefore, in our study, RNA-seq was used to identify and detect the expression of mRNAs, circRNAs and miRNAs in the rat pineal gland between day and night.…”

“…The KEGG pathway analysis revealed several important pathways related to the circadian clock, including the PI3K-Akt signaling pathway, adrenergic signaling in cardiomyocytes and cGMP-PKG signaling pathway. The PI3K-Akt signaling pathway has been shown to be regulated by the clock proteins Cry1, Cry2 and Bmal1, which are part of the oscillations of the transcriptional-translational negative feedback system and regulate the circadian rhythm 43 , 47 , 48 . Mustafa C Beker reported an interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival 49 .…”

Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells

“… 51 , 52 We combined the results obtained from the two algorithms to increase the reliability of the lncRNAs selection procedure as previously reported. 53 …”

Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases

“…CREB is an important transcriptional factor in the regulation of brain-derived neurotrophic factor (BDNF) and with the CREB-BDNF signaling pathway modulating cognitive status and Aβ toxicity in AD [ 172 ]. In the pineal gland of 5xFAD mice, Nam et al [ 105 ] constructed a circRNA-miRNA network with the 10 circRNAs whose expression differences were more significant or whose expression levels were high. From it, a complete ceRNET was established, where circMboat2 and circNlrp5-ps could sponge miR-483 and regulate the expression of Aanat , a critical enzyme for melatonin synthesis [ 173 ].…”