Modification and Expression of mRNA m6A in the Lateral Habenular of Rats after Long-Term Exposure to Blue Light...

Artificial lighting, especially blue light, is becoming a public-health risk. Excessive exposure to blue light at night has been reported to be associated with brain diseases. However, the mechanisms underlying neuropathy induced by blue light remain unclear. An early anatomical tracing study described the projection of the retina to the lateral habenula (LHb), whereas more mechanistic reports are available on multiple brain functions and neuropsychiatric disorders in the LHb, which are rarely seen in epigenetic studies, particularly N6-methyladenosine (m6A). The purpose of our study was to first expose Sprague-Dawley rats to blue light (6.11 ± 0.05 mW/cm², the same irradiance as 200 lx of white light in the control group) for 4 h, and simultaneously provide white light to the control group for the same time to enter a sleep period. The experiment was conducted over 12 weeks. RNA m6A modifications and different mRNA transcriptome profiles were observed in the LHb. We refer to this experimental group as BLS. High-throughput MeRIP-seq and mRNA-seq were performed, and we used bioinformatics to analyze the data. There were 188 genes in the LHb that overlapped between differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis were used to enrich neuroactive ligand-receptor interaction, long-term depression, the cyclic guanosine monophosphate-dependent protein kinase G (cGMP-PKG) signaling pathway, and circadian entrainment. The m6A methylation level of the target genes in the BLS group was disordered. In conclusion, this study suggests that the mRNA expression and their m6A of the LHb were abnormal after blue light exposure during the sleep period, and the methylation levels of target genes related to synaptic plasticity were disturbed. This study offers a theoretical basis for the scientific use of light.