Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Differential Gene Expression between 3×Tg-AD Mice and Se-Met-Treated 3×Tg-AD Mice
2.2. Overrepresentation Analysis
2.3. Real-Time PCR Validation of Differentially Expressed Genes
3. Discussion
3.1. Upregulated Genes in 3×Tg-AD (Se-Met) Mice
3.2. Downregulated Genes in 3×Tg-AD (Se-Met) Mice
4. Material and Methods
4.1. Transgenic Mice
4.2. Tissue Processing
4.3. RNA-Seq Analysis
4.4. Differential Expression Analysis
4.5. Real-Time PCR
4.6. Statistical Analysis
Supplementary Materials
Consent for Publication
Ethics Approval and Consent to Participate
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Category | GO Class | Function | Sample Number | Background Number | p Value | Gene Names |
---|---|---|---|---|---|---|
BP | GO:0052697 | xenobiotic glucuronidation | 4 | 5 | 2.44 × 10−7 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0052696 | flavonoid glucuronidation | 4 | 9 | 1.36 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0009813 | flavonoid biosynthetic process | 4 | 9 | 1.36 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0052695 | cellular glucuronidation | 4 | 10 | 1.89 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0019585 | glucuronate metabolic process | 4 | 11 | 2.56 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0006063 | uronic acid metabolic process | 4 | 11 | 2.56 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0009812 | flavonoid metabolic process | 4 | 11 | 2.56 × 10−6 | Ugt1a2; Ugt1a1; Ugt1a10; Ugt1a6a |
BP | GO:0006805 | xenobiotic metabolic process | 5 | 54 | 4.93 × 10−5 | Ugt1a2; Ugt1a1; Cyp2f2; Ugt1a10; Ugt1a6a |
BP | GO:0071466 | cellular response to xenobiotic stimulus | 5 | 58 | 6.77 × 10−5 | Ugt1a2; Ugt1a1; Cyp2f2; Ugt1a10; Ugt1a6a |
BP | GO:0009410 | response to xenobiotic stimulus | 5 | 64 | 1.04 × 10−4 | Ugt1a2; Ugt1a1; Cyp2f2; Ugt1a10; Ugt1a6a |
CC | GO:0005615 | extracellular space | 25 | 1011 | 7.36 × 10−8 | Pigr; Adcyap1; Tacstd2; Fetub; Pglyrp1; Gpx3; Sftpd; Dmbt1; Pon1; Ces1d; Lbp; Scgb3a1; Mup4; C1s; Bpifb1; Areg; Msln; Anxa1; Tnfsf15; Serpinb11; Bpifa1; Nppa; Il1r1; Scg2; St14 |
CC | GO:0005576 | extracellular region | 52 | 3593 | 6.55 × 10−5 | Pigr; Reg3g; Bpifa1; Tspan1; Tacstd2; Krt14; Ccdc3; Vwf; Fetub; Pglyrp1; Gpx3; Scnn1a; Krt5; Sftpd; Dmbt1; Ces1d; Pon1; Agr2; Obp2a; Cd44; Sult1c1; Lbp; Chi3l4; Scgb3a1; Mup4; Wfdc18; C1s; Gsta3; Muc20; Il1r1; Bpifb1; Krt18; Areg; Wfdc2; Msln; Lypd2; Anxa1; Tnfsf15; Epcam; Serpinb11; Steap4; Slc5a9; Cd177; Clic6; Adcyap1; Ugt1a6a; St14; Tmprss2; Slc44a4; Slc39a4; Scg2; Nppa |
CC | GO:0044421 | extracellular region part | 44 | 3071 | 5.7 × 10−6 | Pigr; Adcyap1; Tspan1; Tacstd2; Krt14; Vwf; Fetub; Pglyrp1; Gpx3; Scnn1a; Krt5; Sftpd; Dmbt1; Ces1d; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Mup4; C1s; Gsta3; Il1r1; Bpifb1; Krt18; Areg; Wfdc2; Msln; Anxa1; Tnfsf15; Epcam; Serpinb11; Steap4; Slc5a9; Cd177; Clic6; Bpifa1; Ugt1a6a; St14; Tmprss2; Slc44a4; Slc39a4; Scg2; Nppa |
CC | GO:0016323 | basolateral plasma membrane | 8 | 176 | 3.91 × 10−5 | Tacstd2; Cd44; St14; Cldn8; Epcam; Cldn7; Muc20; Aqp3 |
CC | GO:0070062 | extracellular vesicular exosome | 32 | 2280 | 1.4 × 10−4 | Pigr; Pglyrp1; Tspan1; Tacstd2; Krt14; Gsta3; Fetub; Scnn1a; Krt5; Dmbt1; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Gpx3; C1s; Vwf; Bpifb1; Krt18; Wfdc2; Anxa1; Epcam; Steap4; Slc5a9; Cd177; Clic6; Ugt1a6a; Tmprss2; Slc44a4; Slc39a4; St14 |
CC | GO:1903561 | extracellular vesicle | 32 | 2280 | 1.41 × 10−4 | Pigr; Pglyrp1; Tspan1; Tacstd2; Krt14; Gsta3; Fetub; Scnn1a; Krt5; Dmbt1; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Gpx3; C1s; Vwf; Bpifb1; Krt18; Wfdc2; Anxa1; Epcam; Steap4; Slc5a9; Cd177; Clic6; Ugt1a6a; Tmprss2; Slc44a4; Slc39a4; St14 |
CC | GO:0043230 | extracellular organelle | 32 | 2284 | 1.44 × 10−4 | Pigr; Pglyrp1; Tspan1; Tacstd2; Krt14; Gsta3; Fetub; Scnn1a; Krt5; Dmbt1; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Gpx3; C1s; Vwf; Bpifb1; Krt18; Wfdc2; Anxa1; Epcam; Steap4; Slc5a9; Cd177; Clic6; Ugt1a6a; Tmprss2; Slc44a4; Slc39a4; St14 |
CC | GO:0065010 | extracellular membrane-bounded organelle | 32 | 2284 | 1.45 × 10−4 | Pigr; Pglyrp1; Tspan1; Tacstd2; Krt14; Gsta3; Fetub; Scnn1a; Krt5; Dmbt1; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Gpx3; C1s; Vwf; Bpifb1; Krt18; Wfdc2; Anxa1; Epcam; Steap4; Slc5a9; Cd177; Clic6; Ugt1a6a; Tmprss2; Slc44a4; Slc39a4; St14 |
CC | GO:0031988 | membrane-bounded vesicle | 35 | 2756 | 4.34 × 10−4 | Pigr; Pglyrp1; Tspan1; Tacstd2; Krt14; Th; Gsta3; Fetub; Gpx3; Scnn1a; Krt5; Dmbt1; Pon1; Cd44; Sult1c1; Lbp; Scgb3a1; Scg2; C1s; Vwf; Bpifb1; Krt18; Wfdc2; Galnt15; Anxa1; Epcam; Steap4; Slc5a9; Cd177; Clic6; Ugt1a6a; Tmprss2; Slc44a4; Slc39a4; St14 |
CC | GO:0098590 | plasma membrane region | 10 | 428 | 8.69 × 10−4 | Aqp3; Cd44; St14; Cldn8; Slc39a4; Scnn1a; Epcam; Cldn7; Muc20; Tacstd2 |
MF | GO:0015020 | glucuronosyltransferase activity | 5 | 74 | 1.99 × 10−4 | Ugt1a2; Ugt1a1; Galnt15; Ugt1a6a; Ugt1a10 |
MF | GO:0008194 | UDP-glycosyltransferase activity | 6 | 135 | 4.03 × 10−4 | Ugt1a2; Galnt15; Ugt1a1; Ugt1a6a; Gal; Ugt1a10 |
MF | GO:0016758 | transferase activity, transferring hexosyl groups | 6 | 165 | 1.11 × 10−4 | Ugt1a2; Galnt15; Ugt1a1; Ugt1a6a; Gal; Ugt1a10 |
MF | GO:0005154 | epidermal growth factor receptor binding | 3 | 30 | 1.4 × 10−3 | Pigr; Cd44; Areg |
MF | GO:0016757 | transferase activity, transferring glycosyl groups | 7 | 243 | 1.62 × 10−3 | St6galnac1; Ugt1a2; Galnt15; Ugt1a1; Ugt1a6a; Gal; Ugt1a10 |
MF | GO:0001972 | retinoic acid binding | 2 | 12 | 3.85 × 10−3 | Ugt1a2; Ugt1a1 |
MF | GO:0019865 | immunoglobulin binding | 2 | 14 | 5.03 × 10−3 | Vwf; Fcamr |
MF | GO:0038024 | cargo receptor activity | 3 | 53 | 6.34 × 10−3 | Ildr1; Tmprss2; Dmbt1 |
MF | GO:0051428 | peptide hormone receptor binding | 2 | 16 | 6.36 × 10−3 | Adcyap1; Nppa |
MF | GO:0033293 | monocarboxylic acid binding | 3 | 55 | 6.9 × 10−3 | Ugt1a2; Ugt1a1; Fabp7 |
Gene Name | Gene Description | logFC | p_Value |
---|---|---|---|
Adcyap1 | adenylate cyclase activating polypeptide 1 | 1.49 | 6.74 × 10−12 |
Areg | amphiregulin | 3.49 | 1.46 × 10−9 |
Scg2 | secretogranin II | 1.02 | 1.51 × 10−7 |
Th | tyrosine hydroxylase | 1.31 | 2.8 × 10−7 |
Fabp7 | fatty acid binding protein 7 | 1.29 | 6.41 × 10−7 |
Pip5k1b | phosphatidylinositol-4-phosphate 5-kinase, type 1 beta | 1.03 | 4.68 × 10−6 |
Trhr2 | thyrotropin releasing hormone receptor 2 | 1.69 | 5.55 × 10−6 |
Etv5 | ets variant 5 | 1.02 | 5.68 × 10−5 |
fantom3_1110005E01 | /// | 1.01 | 1.25 × 10−5 |
Col28a1 | collagen, type XXVIII, alpha 1 | 1.33 | 1.59 × 10−5 |
fantom3_D930027K06 | /// | 1.77 | 1.73 × 10−5 |
fantom3_D930001D16 | /// | 1.77 | 1.73 × 10−5 |
Gm10635 | predicted gene 10635 | 2.91 | 2.09 × 10−5 |
Nppa | natriuretic peptide type A | 1.20 | 2.18 × 10−5 |
Nt5c1a | 5′-nucleotidase, cytosolic IA | 1.36 | 8.67 × 10−5 |
Gal | galanin | 1.48 | 9.23 × 10−5 |
fantom3_A430024L20 | /// | 1.12 | 9.76 × 10−5 |
Rxfp1 | relaxin/insulin-like family peptide receptor 1 | 1.73 | 1.18 × 10−4 |
fantom3_C330006P03 | /// | 1.12 | 1.25 × 10−4 |
Tnfsf15 | tumor necrosis factor (ligand) superfamily, member 15 | 2.76 | 1.33 × 10−4 |
Gene Name | Gene Description | logFC | p_Value |
---|---|---|---|
Lrg1 | leucine-rich alpha-2-glycoprotein 1 | −3.08 | 2.99 × 10−11 |
Anxa1 | annexin A1 | −2.51 | 8.52 × 10−11 |
Cd177 | CD177 antigen | −3.57 | 8.66 × 10−11 |
Vwf | Von Willebrand factor | −1.15 | 2.21 × 10−10 |
Il1r1 | interleukin 1 receptor, type I | −1.26 | 1.35 × 10−9 |
Scgb3a1 | secretoglobin, family 3A, member 1 | −3.75 | 7.5 × 10−8 |
fantom3_1110030K16 | /// | −3.91 | 1.42 × 10−7 |
Abca13 | ATP-binding cassette, sub-family A (ABC1), member 13 | −4.74 | 2.4 × 10−7 |
Pglyrp1 | peptidoglycan recognition protein 1 | −1.61 | 3.23 × 10−7 |
Bpifb1 | BPI fold containing family B, member 1 | −6.70 | 4.13 × 10−7 |
Gpx3 | glutathione peroxidase 3 | −1.90 | 5.13 × 10−7 |
Dlk1 | delta-like 1 homolog (Drosophila) | −2.51 | 5.23 × 10−7 |
Gabrp | gamma-aminobutyric acid (GABA) A receptor, pi | −6.28 | 5.51 × 10−7 |
Serpina3n | serine (or cysteine) peptidase inhibitor, clade A, member 3N | −1.20 | 6.65 × 10−7 |
S100a11 | S100 calcium binding protein A11 | −1.28 | 7.58 × 10−7 |
Muc5b | mucin 5, subtype B, tracheobronchial | −6.35 | 7.95 × 10−7 |
Lypd2 | Ly6/Plaur domain containing 2 | −5.61 | 8.2 × 10−7 |
Pon1 | paraoxonase 1 | −7.07 | 9.8 × 10−7 |
Il18r1 | interleukin 18 receptor 1 | −2.44 | 1.79 × 10−6 |
Ccdc3 | coiled-coil domain containing 3 | −1.41 | 2.03 × 10−6 |
Genes Name | Sequence Information | |
---|---|---|
Adcyap1 | Forward | 5′-GGAGAAAAGTGGAGGGAGCA-3′ |
Reverse | 5′-TGTCTATACCTTTTCCCAAGGACTG-3′ | |
Areg | Forward | 5′-TGGATTGGACCTCAATGACA-3′ |
Reverse | 5′-AGCCAGGTATTTGTGGTTCG-3′ | |
Scg2 | Forward | 5′-CCAATGGTCATGGTATTGACA-3′ |
Reverse | 5′-TTTGCTCCAGAACTCCACAA-3′ | |
Fabp7 | Forward | 5′-AGGCTTTCTGTGCTAC-3′ |
Reverse | 5′-ATTACCGTTGGTTTGG-3′ | |
Evt5 | Forward | 5′-GAAGTGCCTAACTGCCAGTCACCC-3′ |
Reverse | 5′-GGCACCACGCAAGTGTCATCGA-3′ | |
Gal | Forward | 5′-CACTCTGGGACTTGGGATG-3′ |
Reverse | 5′-CAGGC AAGAGGGAGTTACAA-3′ | |
GAPDH | Forward | 5′-CAGCCTCGTCTCATAGACAAGATG-3′ |
Reverse | 5′-CAATGTCCACTTTGTCACAAGAGAA-3′ | |
Lrg | Forward | 5′-GGAGCAGCTATGGTCTCTTG-3′ |
Reverse | 5′-AGTATCAGGCATTCCTTGAG-3′ | |
Scgb3a1 | Forward | 5′-CTCAACCCGCTGAAGCTC-3′ |
Reverse | 5′-CTTCTGGGAGCCCTCTATGA-3′ | |
Pglyrp1 | Forward | 5′-GTGGTGATCTCACACACAGC-3′ |
Reverse | 5′-GTGTGGTCACCCTTGATGTT-3′ |
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Zheng, R.; Zhang, Z.-H.; Zhao, Y.-X.; Chen, C.; Jia, S.-Z.; Cao, X.-C.; Shen, L.-M.; Ni, J.-Z.; Song, G.-L. Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2019, 20, 2998. https://doi.org/10.3390/ijms20122998
Zheng R, Zhang Z-H, Zhao Y-X, Chen C, Jia S-Z, Cao X-C, Shen L-M, Ni J-Z, Song G-L. Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2019; 20(12):2998. https://doi.org/10.3390/ijms20122998
Chicago/Turabian StyleZheng, Rui, Zhong-Hao Zhang, Yu-Xi Zhao, Chen Chen, Shi-Zheng Jia, Xian-Chun Cao, Li-Ming Shen, Jia-Zuan Ni, and Guo-Li Song. 2019. "Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease" International Journal of Molecular Sciences 20, no. 12: 2998. https://doi.org/10.3390/ijms20122998