Dataset Information

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.

ABSTRACT: Objective:The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages. Methods:Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR. Results:In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (STMN1, FGF14, and MAPT) and ?-aminobutyric acid-ergic synapses (GABBR2 and GAD1) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway (NTRK1 and NGFR), autophagy (ATG5), and dopaminergic synapses (AKT1) in the striatum were differentially expressed among control and heroin-treated animals. Conclusion:These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages.

SUBMITTER: Choi MR

PROVIDER: S-EPMC7006971 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.

Choi Mi Ran MR Jin Yeung-Bae YB Bang Sol Hee SH Im Chang-Nim CN Lee Youngjeon Y Kim Han-Na HN Chang Kyu-Tae KT Lee Sang-Rae SR Kim Dai-Jin DJ

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology 20200201 1

<h4>Objective</h4>The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages.<h4>Methods</h4>Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome pr ...[more]

PMID: 31958910

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Project description:BackgroundMouse has been extensively used as a tool for investigating the onset and development of human neurological disorders. As a first step to construct a transgenic mouse model of human brain lesions, it is of fundamental importance to clarify the similarity and divergence of genetic background between non-diseased human and mouse brain tissues.MethodsWe systematically compared, based on large scale integrated microarray data, the transcriptomes of three anatomically distinct brain regions; prefrontal cortex (PFC), hippocampus (HIP) and striatum (STR), across human and mouse. The widely used DAVID web server was used to decipher the biological functions of the highly expressed genes that were identified using a previously reported approach. Venn analysis was used to depict the overlapping ratios of the notably enriched biological process (BP) terms (one-tailed Fisher's exact test and Benjamini correction; adjusted p < 0.01) between two brain tissues. GOSemSim, an R package, was selected to perform GO semantic similarity analysis. Next, we adjusted signal intensities of orthologous genes by the total signals in all samples within species, and used one minus Pearson's correlation coefficient to assess the expression distance. Hierarchical clustering and principal component analysis (PCA) were selected for expression pattern analysis. Lineage specific expressed orthologous genes were identified by comparison of the most extreme sub-datasets across species and further verified using reverse transcription PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR).ResultsWe found that the number of the significantly enriched BP terms of the highly expressed genes in human brain regions is larger than that in mouse corresponding brain regions. The mainly involved BP terms in human brain tissues associated with protein-membrane targeting and selenium metabolism are species-specific. The overlapping ratios of all the significantly enriched BP terms between any two brain tissues across species are lower than that within species, but the pairwise semantic similarities are very high between any two brain tissues from either human or mouse. Hierarchical clustering analysis shows the biological functions of the highly expressed genes in brain tissues are more consistent within species than interspecies; whereas it shows the expression patterns of orthologous genes are evidently conserved between human and mouse equivalent brain tissues. In addition, we identified four orthologous genes (COX5B, WIF1, SLC4A10 and PLA2G7) that are species-specific, which have been widely studied and confirmed to be closely linked with neuro- physiological and pathological functions.ConclusionOur study highlights the similarities and divergences in gene function and expression between human and mouse corresponding brain regions, including PFC, HIP and STR.

Dataset Information

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.

Publications

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.

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