Background
Results and discussion
Temporal distribution of dysregulated genes reveals dramatic changes from M4 onwards
DEG-related functions support alterations in inflammation pathways and behavior
Cortex | Hippocampus | ||||||||
---|---|---|---|---|---|---|---|---|---|
Gene | Probe | M1 | M4 | M6 | M9 | M1 | M4 | M6 | M9 |
Clec7a
| A51P246653 | 0.8 |
12.1
|
35.0
|
30.9
| 1.1 |
15.9
|
32.2
|
32.5
|
Cst7
| A51P137419 | 1.0 |
74.7
|
63.5
|
140.2
| 1.3 |
100.5
|
118.4
|
145.8
|
Itgax
| A51P303424 | 0.7 |
16.3
|
13.4
|
19.6
| 0.8 |
16.1
|
14.8
|
23.2
|
Ccl3
| A51P140710 | 1.0 |
15.8
|
14.7
|
15.4
| 0.6 |
11.3
|
7.3
|
17.3
|
Ccl6
| A51P460954 | 1.4 |
12.4
|
9.4
|
13.4
| 1.4 |
13.7
|
10.8
|
9.7
|
Gfap
| A55P2157245 | 1.1 |
3.4
|
6.1
|
4.4
| 1.1 |
2.2
|
3.0
|
5.4
|
Gfap
| A52P52303 | 1.1 |
5.2
|
8.4
|
5.0
| 1.1 |
2.8
|
3.1
|
4.5
|
Gfap
| A55P2157250 | 1.2 |
8.1
|
8.6
|
11.8
| 0.9 |
4.0
|
8.0
|
3.5
|
Ccl4
| A51P509573 | 0.9 |
9.0
|
7.3
|
9.9
| 0.9 |
12.7
|
10.7
|
11.3
|
Ttr
| A65P19832 |
12.2
|
8.7
|
2.5
| 0.7 | 0.2 | 1.2 | 1.0 |
1.5
|
Kl
| A52P439358 |
2.9
|
3.0
| 1.2 | 0.5 | 0.2 | 1.2 | 0.6 |
2.2
|
Establishment of neuroinflammation through activation of complement
Cortex | Hippocampus | ||||||||
---|---|---|---|---|---|---|---|---|---|
Gene | Probe | M1 | M4 | M6 | M9 | M1 | M4 | M6 | M9 |
Itgam
| A55P1977929 | 0.9 |
1.5
| 1.2 |
1.9
| 1.1 |
2.0
|
1.8
|
1.6
|
Itgb2
| A51P262208 | 1.0 |
2.5
|
2.6
|
3.4
| 1.0 |
2.3
|
2.4
|
2.5
|
Itgb3
| A52P553890 | 0.9 | 1.3 |
2.0
|
1.5
| 0.9 |
1.8
|
1.9
|
3.0
|
Tlr2
| A51P452629 | 1.0 |
2.7
|
3.6
|
3.3
| 0.6 |
3.2
|
3.6
|
5.1
|
C3
| A51P110301 |
1.6
| 1.0 |
3.5
|
1.6
| 0.9 | 1.2 |
5.2
|
6.3
|
C4b
| A55P2078633 | 1.1 |
2.6
|
9.0
|
3.7
| 0.8 |
2.6
|
4.0
|
5.6
|
C1qa
| A51P181451 | 1.1 |
2.6
|
3.2
|
4.0
| 1.0 |
3.0
|
3.8
|
4.7
|
C1qb
| A51P351860 | 1.0 |
2.3
|
2.9
|
3.2
| 1.0 |
2.6
|
5.1
|
2.9
|
C1qc
| A51P102789 | 1.0 |
2.8
|
2.0
|
5.7
| 1.2 |
3.0
|
4.6
|
4.2
|
Altered expression of interferon gamma-induced genes
Cortex | Hippocampus | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Gene | Probe | M1 | M4 | M6 | M9 | M1 | M4 | M6 | M9 | |
Gusb
| A51P211491 | 0.9 |
2.5
|
3.2
|
3.2
| 1.1 |
3.0
|
3.6
|
3.9
|
Lysosomal biogenesis
|
Naglu
| A52P504361 | 1.0 |
2.1
|
2.1
|
2.2
| 0.8 |
1.7
|
2.2
|
2.0
| |
Hexa
| A51P282667 | 1.1 |
1.9
|
2.0
|
2.3
| 1.2 |
1.7
|
2.3
|
2.4
| |
Hexb
| A51P453111 | 1.0 |
2.5
|
2.0
|
3.2
| 0.9 |
2.8
|
2.0
|
3.3
| |
Ctsd
| A65P13209 | 1.1 |
3.0
|
4.4
|
2.4
| 0.9 |
2.8
|
3.8
|
3.1
| |
Tgfb1
| A51P390715 | 1.1 |
1.8
|
1.7
|
2.3
| 0.8 |
2.3
|
2.6
|
1.6
|
TGF-β signaling
|
Tgfbr1
| A51P2137206 | 1.1 |
1.5
|
1.7
|
1.7
| 0.8 |
1.6
| 1.4 |
1.9
| |
Tgfbr2
| A51P450573 | 1.0 |
1.9
|
2.1
|
2.3
| 1.0 |
2.2
|
2.0
|
3.7
| |
Aif1
| A51P400543 | 1.0 |
2.1
|
2.4
|
2.2
| 1.0 |
2.5
|
2.3
|
2.9
|
Markers of microglial activation
|
Ptprc
| A55P1990324 | 1.0 |
2.0
|
1.7
|
2.0
| 1.0 |
2.0
|
2.1
|
2.5
| |
Cd86
| A55P1971951 | 0.9 |
1.8
|
2.3
|
2.5
| 1.1 |
2.5
|
3.0
|
3.5
| |
Cd14
| A51P172853 | 1.0 |
2.7
|
3.2
|
3.8
| 1.0 |
2.6
|
3.6
|
3.3
| |
Igf1
| A55P2031631 | 0.9 |
2.6
|
2.0
|
5.1
| 1.0 |
3.0
|
3.0
|
4.2
|
Protective activities
|
Osmr
| A51P319460 | 0.9 |
1.6
|
2.7
|
3.1
| 0.7 |
2.5
|
3.0
|
5.3
| |
Grn
| A51P192800 | 0.9 |
2.5
|
2.3
|
2.6
| 1.1 |
2.2
|
3.0
|
2.5
|
Potential role of IRF8 in the expression of interferon gamma-regulated genes
Involvement of NADPH oxidase (NOX) complex in microglial activation
Microglial phagocytosis
Other neuroprotective activities
Limitations of the study
Materials and methods
Animals
RNA isolation
Real-time quantitative PCR (qPCR)
qPCR | Microarray | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Age | Gene | Wt 1 | Wt 2 | Wt 3 | Tg 1 | Tg 2 | Tg 3 | Fold change Tg/Wt | Wt | Tg | Fold change Tg/Wt |
M1 |
Aif1
| 1.3 | 0.9 | 0.8 | 1.3 | 1.3 | 0.9 |
1.2
| 2098.9 | 2010.3 |
1.0
|
Gfap
| 1.5 | 0.9 | 0.7 | 1.3 | 1.4 | 0.8 |
1.2
| 6320.3 | 6827.6 |
1.1
| |
M4 |
Aif1
| 1.1 | 1.1 | 0.9 | 2.8 | 1.7 | 1.3 |
3.1
| 2171.1 | 5335.4 |
2.5
|
Gfap
| 0.9 | 1.3 | 0.9 | 5.5 | 6.1 | 5.1 |
5.5
| 5381.9 | 15329.9 |
2.9
| |
M6 |
Aif1
| 0.9 | 1.0 | 1.2 | 2.8 | 1.7 | 1.3 |
1.9
| 2427.4 | 5530.1 |
2.3
|
Gfap
| 1.1 | 1.0 | 0.9 | 3.9 | 5.6 | 4.2 |
4.5
| 5694.4 | 17759.7 |
3.1
| |
M9 |
Aif1
| 1.4 | 0.9 | 0.8 | 2.6 | 2.0 | 2.3 |
2.3
| 2551.1 | 7422.3 |
2.9
|
Gfap
| 1.5 | 0.8 | 0.9 | 5.0 | 7.0 | 5.9 |
5.9
| 5172.5 | 23062.3 |
4.5
|