Immunohistochemical distributions of GFAP in the cingulum. Untreated control animal (left), MMI-treated animal (right). 200× magnification. Graph shows the mean number of positive cells within the cingulum at 100× magnification (untreated controls: n = 6, MMI and PTU groups: n = 10).
* and ** P < 0.05, 0.01 vs. untreated controls (Dunnett’s test or Dunnett-type rank-sum test).
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Table 3-1. List of genes commonly up-regulated in the microdissected cerebral white matter region after exposure to DBDE at 10, 100, and 1,000 ppm (≥ 2-fold)
Accession no. Gene title Symbol DBDE
10 ppm 100 ppm 1000 ppm Up-regulated (129genes)
XM_002725261 Similar to KB07 protein RGD1561940 5.42 15.74 14.96
AI176450 EST – 3.60 11.22 12.26
AI237569 EST – 6.60 7.79 12.06
NM_012718 androgen regulated 20 kDa protein Andpro 4.36 5.97 11.48
NM_145879 suppressor of cytokine signaling 1 Socs1 3.19 4.90 11.25
NM_001108693 retinol binding protein 7, cellular Rbp7 3.41 13.75 10.17
AI712659 EST – 2.48 3.66 9.02
NM_001108617 PFTAIRE protein kinase 1 Pftk1 2.57 2.32 6.57
NM_031502 amylase 2 Amy2 6.73 3.92 6.36
XM_002725036 Leucine rich repeat containing 3B Lrrc3b 2.67 2.61 6.36
BM385169 EST – 4.47 2.33 6.25
AI502924 EST – 2.22 5.65 6.20
NM_173309 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2
Elavl2 3.97 2.11 6.02
NM_001101680 forkhead box C2 Foxc2 3.11 2.55 5.83
AW523012 EST – 2.05 2.14 5.75
NM_001025051 family with sequence similarity 110, member C Fam110c 6.00 8.02 5.64
BF394267 EST – 2.44 6.25 5.55
BI295646 EST – 2.06 4.09 5.52
AA893529 EST – 2.59 3.54 5.41
NM_001025740 ribonucleotide reductase M2 Rrm2 2.20 2.10 5.39
AF053092 EST – 2.80 5.63 5.34
NM_001106908 similar to RIKEN cDNA 4832428D23 gene RGD1561425 2.19 4.04 5.21
NM_138879 selectin E Sele 4.85 3.72 5.13
NM_030985 angiotensin II receptor, type 1a Agtr1a 2.57 9.55 5.10
NM_181440 glutamine/glutamic acid-rich protein A Grpca 3.05 4.04 5.02
BF288392 EST – 2.29 7.03 4.99
NM_001107058 mitogen activated protein kinase kinase kinase
3 Map3k3 2.86 2.36 4.96
NM_001109226 Proline-rich transmembrane protein 4 Prrt4 3.01 5.52 4.94
NM_001013079 oxysterol binding protein-like 2 Osbpl2 2.78 6.87 4.88
NM_001136151 neuregulin 2 Nrg2 2.61 3.91 4.84
AI072042 EST – 3.55 2.73 4.81
AI385307 EST – 2.46 2.06 4.72
AI535212 EST – 2.15 5.15 4.69
AI113065 EST – 2.84 7.40 4.63
AW528250 EST – 2.32 2.49 4.59
NM_001173426 RNA binding protein with multiple splicing 2 Rbpms2 3.24 5.76 4.53
NM_053986 myosin Ib Myo1b 2.10 3.56 4.53
BE104268 EST – 2.07 2.86 4.52
NM_001037357 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 3-like
Lilrb3l 2.72 2.69 4.41
AI639063 EST – 4.04 4.29 4.37
NM_001108394 zinc finger, CCHC domain containing 24 Zcchc24 3.01 3.96 4.36
120
NM_012620 serine (or cysteine) peptidase inhibitor, clade E,
member 1 Serpine1 2.75 4.72 4.34
AI102874 EST – 2.18 6.65 4.30
BF396605 EST – 2.23 3.66 4.25
NM_012596 leptin receptor Lepr 2.26 3.54 4.23
NM_001135877 TAF7-like RNA polymerase II, TATA box
binding protein (TBP)-associated factor Taf7l 2.59 4.56 4.20
NM_198735 ADP-ribosyltransferase 2b Art2b 2.20 2.06 4.20
NM_001109304 cripto, FRL-1, cryptic family 1 Cfc1 3.24 3.19 4.10
BF396608 EST – 2.00 3.32 4.07
NM_001009691 Doublecortin-like kinase 2 Dclk2 2.42 4.02 4.05
NM_019236 hairy and enhancer of split 2 Hes2 3.63 2.35 4.03
NM_017001 erythropoietin Epo 3.58 3.25 4.02
NM_001025013 melanoma antigen family B, 16 Mageb16 2.40 2.46 4.01
NM_017144 troponin I type 3 Tnni3 4.51 3.15 4.01
AI059493 EST – 2.27 2.18 4.00
AI706203 EST – 2.66 3.73 3.98
BF288661 EST – 4.32 3.76 3.97
NM_001107025 abhydrolase domain containing 15 Abhd15 2.49 8.15 3.91
AA955915 EST – 2.71 2.71 3.87
BE096287 EST – 2.44 2.01 3.87
AI030285 EST – 2.65 2.23 3.87
NM_001107097 zinc finger and BTB domain containing 11 Zbtb11 2.59 2.89 3.85
NM_001107413 iroquois homeobox 3 Irx3 2.42 4.11 3.79
AW527665 EST – 2.70 2.31 3.78
BF391952 EST – 2.14 5.61 3.70
BF392832 EST – 6.00 2.82 3.63
AA859474 EST – 4.11 6.71 3.61
NM_173110 prolactin family 8, subfamily a, member 5 Prl8a5 5.16 3.64 3.60
XM_001055799 EST – 2.03 4.01 3.57
NM_183331 coagulation factor VIII, procoagulant
component F8 2.87 2.71 3.53
XM_001069604 smoothelin-like 1 Smtnl1 2.30 2.40 3.52
NM_024353 phospholipase C, beta 4 Plcb4 2.54 2.14 3.50
NM_134384 spermatogenesis associated 19 Spata19 2.67 2.59 3.50
NM_001024786 WD repeat domain 78 Wdr78 2.19 4.40 3.49
BF415997 EST – 2.26 3.46 3.44
NM_001108251 Ubiquilin 2 Ubqln2 2.77 7.77 3.35
BF416277 EST – 2.00 3.93 3.30
NM_053704 BCL2-interacting killer Bik 2.84 3.94 3.23
NM_012841 deleted in colorectal carcinoma Dcc 3.30 2.75 3.17
NM_021837 myc-like oncogene, s-myc protein Mycs 3.39 2.96 3.10
XM_001056035 forkhead box I2 Foxi2 3.99 3.48 3.08
AI113090 EST – 3.87 2.45 3.05
NM_138978 prokineticin receptor 2 Prokr2 2.76 2.06 3.04
AW534043 EST – 2.24 3.45 2.97
NM_001106490 myosin binding protein C Mybpc3 2.05 3.28 2.96
XM_002726010 EST – 2.39 2.05 2.96
NM_053708 gastrulation brain homeobox 2 Gbx2 2.43 2.59 2.93
BF403955 EST – 2.93 3.11 2.92
121
NM_012770 guanylate cyclase 1, soluble, beta 2 Gucy1b2 2.15 6.00 2.90
NM_152936 serine peptidase inhibitor, Kazal type 1 Spink1 2.53 3.56 2.89
NM_019374 prodynorphin Pdyn 2.80 3.59 2.88
NM_012684 variable coding sequence A1 Vcsa1 4.80 8.64 2.79
NM_001129878 Homeo box A10 Hoxa10 2.32 2.58 2.79
BI290864 EST – 2.04 3.41 2.78
NM_001109257 kelch domain containing 5 Klhdc5 2.13 2.70 2.77
NM_173322 proline-rich nuclear receptor coactivator 1 Pnrc1 2.77 5.68 2.75
AI011647 EST – 2.42 4.75 2.74
NM_001106024 phosphodiesterase 6B, cGMP-specific, rod, beta Pde6b 2.90 3.69 2.71
XM_001069645 EST – 5.01 4.69 2.71
BF401369 EST – 2.23 2.76 2.66
NM_001110490 LIM domain binding 3 Ldb3 2.24 2.77 2.63
NM_001177682 purinergic receptor P2Y, G-protein coupled, 10 P2ry10 2.58 4.27 2.61
AI502559 EST – 2.33 2.06 2.60
NM_053818 solute carrier family 6 (neurotransmitter
transporter, glycine), member 9 Slc6a9 2.21 3.11 2.60
BF410362 EST – 2.82 3.72 2.54
XM_002729411 EST – 2.33 3.38 2.48
NM_138836 protease, serine, 8 Prss8 2.12 2.12 2.48
NM_001107804 Molybdenum cofactor synthesis 3 Mocs3 4.36 2.98 2.48
BE120031 EST – 2.22 2.80 2.43
NM_139113 nuclear receptor subfamily 2, group F, member 6
Nr2f6 3.32 2.84 2.43
BF399574 EST – 2.49 6.21 2.42
NM_001134598 EST – 2.40 2.22 2.41
AW920335 EST – 2.19 2.17 2.41
NM_001127683 heat shock transcription factor 2 binding protein Hsf2bp 2.67 3.11 2.41
AW921534 EST – 2.13 2.27 2.40
XM_001066131 EST – 2.84 2.88 2.36
NM_017023 potassium inwardly-rectifying channel,
subfamily J, member 1 Kcnj1 3.35 2.27 2.27
NM_022379 transcription factor EC Tfec 2.27 2.67 2.27
XR_085738 family with sequence similarity 184, member A Fam184a 2.23 2.23 2.23
BF414624 EST – 2.54 2.00 2.23
NM_053629 follistatin-like 3 Fstl3 2.56 2.51 2.19
BF400760 EST – 2.08 6.58 2.15
NM_001108497 EST – 2.35 2.27 2.15
BF400813 EST – 2.21 2.57 2.05
BF400843 EST – 2.38 4.12 2.04
AI237240 EST – 2.22 2.42 2.03
NM_001033955 calcitonin-related polypeptide alpha Calca 2.10 2.78 2.03
BF403851 EST – 2.26 2.85 2.03
BF396335 EST – 2.50 2.61 2.01
Abbreviations: DBDE, decabromodiphenyl ether; EST, expressed sequence tag.
122
Table 3-2. List of genes commonly down-regulated in the microdissected cerebral white matter region after exposure to DBDE at 10, 100, and 1,000 ppm (≤ 0.5-fold)
Accession no. Gene title Symbol DBDE
10 ppm 100 ppm 1000 ppm Down-regulated (16 genes)
NM_001025420 lymphocyte-specific protein 1 Lsp1 0.18 0.11 0.16
NM_172222 complement component 2 C2 0.46 0.27 0.17
AW142962 EST – 0.19 0.45 0.22
BF403278 EST – 0.45 0.33 0.23
BI291223 EST – 0.46 0.35 0.24
NM_145672 chemokine (C-X-C motif) ligand 9 Cxcl9 0.48 0.31 0.27
AA892204 EST – 0.29 0.34 0.28
BI290841 EST – 0.47 0.35 0.30
BF416112 EST – 0.39 0.37 0.31
NM_130424 transmembrane protease, serine 2 Tmprss2 0.43 0.23 0.32
AI058852 EST – 0.36 0.30 0.35
NM_147135 SH3-binding domain kinase 1 Sbk1 0.22 0.30 0.36
NM_001007684 Kruppel-like factor 2 Klf2 0.41 0.36 0.38
NM_022707 phospholamban Pln 0.25 0.24 0.38
BE100194 EST – 0.44 0.37 0.40
BF567236 EST – 0.45 0.43 0.45
Abbreviations: DBDE, decabromodiphenyl ether; EST, expressed sequence tag.
123
Table 3-3. List of genes commonly up-regulated in the microdissected cerebral white matter region after exposure to DBDE at 100 and 1,000 ppm (≥ 2-fold)
Accession no. Gene title Symbol DBDE
10 ppm 100 ppm 1000 ppm Up-regulated (669genes)
NM_001191992 outer dense fiber of sperm tails 3B Odf3b 1.55 5.87 29.88
BI288579 EST – 1.18 84.91 27.81
NM_001106602 deoxyguanosine kinase Dguok 0.82 28.19 24.35
XR_085573 similar to mKIAA1783 protein RGD1560214 0.63 9.81 15.39
BM390363 EST – 0.82 2.20 12.46
NM_031686 sodium channel, voltage-gated, type VII, alpha Scn7a 0.89 7.34 11.60 NM_001191598 coiled-coil domain containing 113 Ccdc113 1.33 2.08 11.31
BE113493 EST – 0.64 12.08 11.20
NM_021666 triadin Trdn 1.38 5.40 10.88
XM_002725158 Hypothetical LOC290577 LOC290577 1.43 3.86 10.76
BM386877 EST – 1.65 5.38 10.34
NM_138884 aldo-keto reductase family 1, member D1 (delta 4-3-ketosteroid-5-beta-reductase)
Akr1d1 1.64 10.18 10.25 NM_022928 G protein-coupled receptor kinase 4 Grk4 0.61 4.57 9.86 NM_031635 fucosyltransferase 2 (secretor status included) Fut2 1.14 5.31 9.83 XM_001061953 Similar to paired immunoglobin-like type 2 receptor
alpha LOC685020 1.72 10.32 9.74
AW433528 EST – 1.02 5.75 9.32
AI010736 EST – 1.13 6.35 9.10
NM_024365 5-hydroxytryptamine (serotonin) receptor 6 Htr6 1.15 14.58 8.69 NM_001033073 defensin alpha-related sequence 1 Defa-rs1 1.05 6.78 8.61
AI233574 EST – 1.74 4.29 8.20
NM_001135807 H2A histone family, member Y2 H2afy2 1.45 3.10 8.06
NM_139184 proline-rich glycoprotein (sgp158) Sgp158 1.77 6.77 7.93
NM_001141935 ATPase, class V, type 10A Atp10a 1.50 7.61 7.67
XM_001061900 histone cluster 1, H4m Hist1h4m 1.87 5.14 7.57
NM_001106689 Zinc finger protein 593 Znf593 1.01 5.07 7.45
NM_001009920 glutathione S-transferase Yc2 subunit Gsta5 1.03 2.42 7.39
NM_001191758 cache domain containing 1 Cachd1 1.19 6.53 7.22
AA893390 EST – 0.54 2.68 7.19
XM_001058380 Hypothetical protein LOC680687 LOC680687 1.44 5.41 7.16
BE119818 EST – 1.35 7.87 7.12
XR_085609 hypothetical LOC100363796 LOC100363796 0.92 2.13 7.07
AI598332 EST – 1.02 2.19 6.96
NM_147213 alpha-2u globulin PGCL5 LOC259245 1.98 3.02 6.93
NM_001033964 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2
Pfkfb2 1.92 6.05 6.89
BF410174 EST – 1.09 2.76 6.86
XR_085950 similar to Gene model 784 RGD1561693 1.51 5.62 6.85
BI282568 keratinocyte differentiation associated protein Krtdap 1.18 5.46 6.83
BF420118 EST – 1.07 4.91 6.74
AI008553 EST – 1.88 3.64 6.71
NM_001025417 actin-like 7b Actl7b 1.66 6.41 6.71
AA850953 EST – 0.78 10.18 6.61
XM_001059437 Methyl-CpG binding domain protein 4 Mbd4 1.97 5.69 6.58