Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis

Abstract

Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA–DEmiRNA–DEmRNA and DElncRNA–DEmiRNA–DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI.

Identification of hub genes and potential mechanisms that linked hyperbaric oxygen therapy to traumatic injury Using Bioinformatics Analysis

“…Currently, several researchers have used bioinformatics methods to explore hub genes and key pathways associated with TBI and veri ed that melatonin and Xuefu Zhuyu decoction exerts neuroprotective effects on mice with TBI in the subacute phase. Therefore, bioinformatics analyses are helpful for identifying disease-related pathogenic mechanisms [11][12][13].…”

LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD

“…Non-coding RNAs (ncRNAs) constitute the majority of the human transcribed genome. Increasing evidence suggests that post-transcriptional mechanisms, including ncRNAs, are crucial in regulating the expression of circadian genes within the pineal gland (Zhou et al 2019a , b ; Fu et al 2022 ). Notably, miR-182 and miR-483, abundantly expressed in the pineal gland, target key regulators of the biological clock, namely Clock and Aanat (a rate-limiting enzyme involved in melatonin synthesis), respectively (Ding et al 2015 ; Clokie et al 2012 ).…”