563. LARGE-SCALE PROFILING OF CODING AND LONG NONCODING TRANSCRIPTOMES IN THE HIPPOCAMPUS OF MICE ACUTELY EXPOSED TO VAPORIZED THC

Abstract Background The rising popularity of delta-9-tetrahydrocannabinol (THC) vaping has raised public health concerns due to its association with adverse neurological, respiratory, and cognitive effects. Unlike traditional cannabis consumption methods, vaping delivers concentrated THC rapidly to the bloodstream, increasing its potential to affect brain regions, such as the hippocampus. Aims & Objectives This study aimed to investigate the differential expressions of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus following acute THC exposure via vaping. Method ICR male mice were acutely exposed to vaporized 50 mg THC (n = 5, THC group) or oil (n = 5, control group). Large-scale transcriptome profiling of the hippocampus was performed using total RNA sequencing, and gene ontology (GO) enrichment analysis was conducted. Among the transcripts with more than a 2-fold change, some were validated using real-time RT-PCR. Results Compared to the control group, 89 lncRNAs were upregulated and 264 were downregulated in the THC group. Among the 16 lncRNAs with more than a 2-fold significant change identified through transcriptome profiling in the THC group, validation revealed that 3 lncRNAs were significantly upregulated, while 12 lncRNAs were significantly downregulated. Of 929 mRNAs differentially expressed in THC group compared to the control group, 366 were upregulated and 563 were downregulated in the THC group. Based on the results of GO enrichment, upregulated mRNAs were significantly enriched in biological process (BP) associated with glutamatergic synaptic transmission, synaptic modulation, and excitatory postsynaptic potential. On the other hands, downregulated mRNAs were significantly enriched in BP associated with dendrite morphogenesis, brain development, chemical synaptic transmission, and neuromuscular synaptic transmission. As a result of validating 23 mRNAs included in the BP, 10 mRNAs including Grin2a, Gria3, and Camk2g related to glutamatergic synaptic transmission were significantly upregulated, while 10 mRNAs including Drd1, Drd2, Gnal, and Adcy5 related to dopaminergic synapse were significantly downregulated. Interestingly, among the validated lncRNAs and mRNAs, NONMMUT004928.2 and Drd2, as well as NONMMUT057101.2 and Adcy5, showed a strong and significant correlation (Pearson correlation > 0.95). Discussion & Conclusions These findings provide novel insights into THC-induced transcriptomic changes in the hippocampus, suggesting potential mechanisms underlying synaptic modulation and neuronal function disruption. The strong correlations between specific lncRNAs and mRNAs highlight their potential as biomarkers and therapeutic targets for THC-induced cognitive and neuropsychiatric disorders.