Mi Ran Choi, Yeung-Bae Jin, Sol Hee Bang, Chang-Nim Im, Youngjeon Lee, Han-Na Kim, Kyu-Tae Chang, Sang-Rae Lee, Dai-Jin Kim. Clin Psychopharmacol Neurosci 2020;18:93-108. https://doi.org/10.9758/cpn.2020.18.1.93

Objective Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs.Methods After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry.Results The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group.Conclusion These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E₂ (PGE₂) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.

Excessive use of alcohol can induce neurobiological and neuropathological alterations in the brain, including the hippocampus and forebrain, through changes in neurotransmitter systems, hormonal systems, and neuroimmune processes. We aimed to investigate the effects of ethanol on the expression of coding and noncoding RNAs in a brain-derived cell line exposed to ethanol. After exposing Neuro2a cells, a neuroblastoma cell line, to ethanol for 24 and 72 h, we observed cell proliferation and analyzed up- and downregulated mRNAs and long noncoding RNAs (lncRNAs) using total RNA-Seq technology. We validated the differential expression of some mRNAs and lncRNAs by RT-qPCR and analyzed the expression of Cebpd and Rnu3a through knock-down of Cebpd. Cell proliferation was significantly reduced in cells exposed to 100 mM ethanol for 72 h, with 1773 transcripts up- or downregulated by greater than three-fold in ethanol-treated cells compared to controls. Of these, 514 were identified as lncRNAs. Differentially expressed mRNAs and lncRNAs were mainly observed in cells exposed to ethanol for 72 h, in which Atm and Cnr1 decreased, but Trib3, Cebpd, and Spdef increased. On the other hand, lncRNAs Kcnq1ot1, Tug1, and Xist were changed by ethanol, and Rnu3a in particular was greatly increased by chronic ethanol treatment through inhibition of Cebpd. Our results increase the understanding of cellular and molecular mechanisms related to coding and noncoding RNAs in an in vitro model of acute and chronic exposure to ethanol.

Abnormal epigenetic reprogramming of nuclear-transferred (NT) embryos leads to the limited efficiency of producing cloned animals. Trichostatin A (TSA), a histone deacetylase inhibitor, improves NT embryo development, but its role in histone acetylation in porcine embryos cloned with mesenchymal stem cells (MSCs) is not fully understood. This study aimed to compare the effects of TSA on embryo development, histone acetylation patterns, and key epigenetic-related genes between in vitro fertilization (IVF), NT-MSC, and 40 nM TSA-treated NT-MSC (T-NT-MSC). The results demonstrated an increase in the blastocyst rate from 13.7% to 32.5% in the T-NT-MSC, and the transcription levels of CDX2, NANOG, and IGF2R were significantly elevated in T-NT-MSC compared to NT-MSC. TSA treatment also led to increased fluorescence intensity of acH3K9 and acH3K18 during early embryo development but did not differ in acH4K12 levels. The expression of epigenetic-related genes (HDAC1, HDAC2, CBP, p300, DNMT3a, and DNMT1) in early pre-implantation embryos followed a pattern similar to IVF embryos. In conclusion, TSA treatment improves the in vitro development of porcine embryos cloned with MSCs by increasing histone acetylation, modifying chromatin structure, and enhancing the expression of key genes, resulting in profiles similar to those of IVF embryos.