)| PMID |
16737688 ( ) |
|---|---|
| Title | Ascending neuropathology in the CNS of a mutant SOD1 mouse model of amyotrophic lateral sclerosis. |
| Abstract | Transgenic mice expressing a mutated human Cu/Zn superoxide dismutase (SOD1) gene develop a motor neuron disease similar to familial amyotrophic lateral sclerosis (FALS). While the histopathology and the inflammatory reactions in the spinal cord of these mice are well described, their spatiotemporal extension into brain areas and the relationship between degenerative and inflammatory events remain obscure. In the present study, we investigated the time course and extent of degenerative changes and inflammatory reactions in the CNS during progression of the disease in a transgenic FALS model, the SOD1-G93A mouse with histological and immunohistochemical methods. Compared to non-transgenic littermates, the SOD1-G93A transgenics developed widespread degeneration in both motor and extra-motor regions up to telencephalic regions, including the cerebral cortex but sparing distinct regions like the striatum and hippocampus. We provide evidence that these degenerative processes are accompanied by intense inflammatory reactions in the brain, which spatiotemporally correlate with degeneration and comprise besides strong astro- and microgliotic reactions also an influx of peripheral immune cells such as T-lymphocytes and dendritic cells. Both degeneration and inflammatory reactions spread caudocranially, starting at 2 months in the spinal cord and reaching the telencephalon at 5 months of age. Since the corticospinal tract lacked any signs of degeneration, we conclude that the upper and the lower motor neurons degenerate independently of each other. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 28 | SOD1 | SOD1- | |
| 4235 | GFAP | glial fibrillary acidic protein | 9 | GFAP- | glial fibrillary acidic protein | |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | 7 | CD11c | CD11c-positive | integrin alpha x | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 4 | caspase 3 | |
| 11782 | TH | tyrosine hydroxylase | 3 | tyrosine 3 monooxygenase | tyrosine hydroxylase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | expressing a mutated human Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 gene develop a motor neuron disease similar to familial amyotrophic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | a mutant form of Cu/Zn Cu Zn superoxide dismutase (SOD1; SOD1 Rosen 1993 that normally functions in the regulation of oxidative |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Mutant SOD1 produces motor neuron injury by a toxic gain of function |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Now that _amp_#x3e 90 different SOD1 mutations have been described transgenic mouse models with these mutations |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Overexpression of the human Glycine 93_amp_#xa0 _amp_#x2192 _amp_#xa0 Alanine SOD1 mutation (SOD1-G93A) SOD1-G93A causes a phenotype that closely mimics the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | copies ( Gurney et al. 1994 of the human mutant SOD1 gene (Cu/Zn-SOD) Cu Zn-SOD containing the Gly 93 _amp_#xa0 _amp_#x2192 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | (PCR) PCR of tail DNA with primers specific for human SOD1 gene |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | SOD1 transgenics died between 5 and 6_amp_#xa0 months of age |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | FluoroJade and silver staining as well as SOD1- and tyrosine hydroxylase-IHC (see see below were used to identify |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Primary antibodies were used to further evaluate neurodegenerative alterations (SOD1 SOD1 and tyrosine hydroxylase to identify the molecular changes associated with |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c | 1.9 | acidic protein T-cells (T-cell-receptor T-cell-receptor CD3 and dendritic cells (CD11c) CD11c |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c | 1.9 | Immunohistochemical stainings (IHC) IHC were performed either on cryostate (CD11c; CD11c Casp3act or on paraffin sections after deparaffinization and antigen retrieval |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | in 0.01_amp_#xa0 M citrate buffer pH 6.0 for CD3 PT66 SOD1 TH |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | Morphological signs of degeneration were semi-quantitatively evaluated in SOD1- or TH (for for catecholaminergic neurons -immunostained and in Gallyas-stained |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | SOD1 and TH immunoreactivities were observed throughout cellular somata and processes |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP- | 2.5 | For analysis of gliosis the staining intensity in GFAP- and PT66-immunostained sections and the number of CD3- CD11c- and |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c- | 1.9 | in GFAP- and PT66-immunostained sections and the number of CD3- CD11c- and TB/Pin-positive TB Pin-positive cells were evaluated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | The morphological changes in SOD1- or TH-stained sections the amount of Gallyas-positive structures and the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Fig 2._amp_#xa0 Gallyas (A, A B D_amp_#x2013 K and SOD1 staining (C) C in transgenics at the age of 2_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | F H either silver-stained (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, G H |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | SOD1 immunostaining reveals vacuolar changes already in 3-month-old transgenics (arrows) arrows |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | Immunostainings for GFAP and PT66 show abundant reactive astrocytes and microglial cells at |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | (A_amp_#x2013;C) A_amp_#x2013 C or immunostained for TH (D_amp_#x2013;F), D_amp_#x2013 F GFAP (G_amp_#x2013;I) G_amp_#x2013 I and PT66 (J_amp_#x2013;L) J_amp_#x2013 L |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | F H either silver-stained (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, G H |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | arrows in panel C are visible at 4_amp_#xa0 months after SOD1 immunostaining (C), C while Gallyas staining is negative (A) A |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | astrogliosis and microgliosis appear in this region as visualized by GFAP and PT66 immunostaining |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c-positive | 1.9 | Fig 6._amp_#xa0 Localization of CD3-positive T-cells (A) A and CD11c-positive dendritic cells (B_amp_#x2013;D) B_amp_#x2013 D in the locus coeruleus (A), |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | The SOD1 transgenics showed first signs of hindlimb paresis at 3.5_amp_#x2013 5_amp_#xa0 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | motor activity progressively decreased and at 3.5_amp_#xa0 months of age SOD1 transgenics were significantly ( P _amp_#xa0 _amp_#x2264 _amp_#xa0 0.05 less |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Most of the SOD1 immunoreactivity was observed in the cytoplasm although less intense staining |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | Both SOD1- and TH-ip cells appeared morphologically unaltered in non-transgenic animals |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | describe chronologically the degenerative changes and inflammatory reactions in the SOD1 transgenics while the figures and tables illustrate the pathological changes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | In the SOD1 transgenics the first morphological signs of degeneration were notable by |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | At the age of 3_amp_#xa0 months SOD1- and TH-IHC revealed pathological alterations of the neuropil in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 3.2 | In addition SOD1-/TH-IHC SOD1- TH-IHC pointed out lesions in the neuropil of the ventral |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | Immunostainings with the antibodies GFAP and PT66 revealed an increase in glial cell number and |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | Surprisingly no differences in PT66 and GFAP staining patterns between transgenics and littermates were found in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 4.2 | Despite the close similarities between the histopathology of transgenic SOD1 mice and ALS the experimental model departs from the human |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c | 1.9 | The integrin alpha X subunit (CD11c) CD11c is a known marker for dendritic cells (DC) DC ( |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | CD11c | 1.9 | However recent publications reported CD11c expression on a subset of cytotoxic T-cells in the intestine |
| 11782 | TH | tyrosine hydroxylase | tyrosine hydroxylase | 1.0 | fluorojade and silver staining as well as sod1 and tyrosine hydroxylase ihc see below were used to identify degenerative changes. |
| 11782 | TH | tyrosine hydroxylase | tyrosine hydroxylase | 1.0 | primary antibodies were used to further evaluate neurodegenerative alterations sod1 and tyrosine hydroxylase to identify the molecular changes associated with degeneration caspase 3 active and to characterize the immune reaction. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | primary antibodies were used to further evaluate neurodegenerative alterations sod1 and tyrosine hydroxylase to identify the molecular changes associated with degeneration caspase 3 active and to characterize the immune reaction. |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | therefore we focused on the major participants in the immune response microglia/macrophages phosphotyrosine a specific and excellent marker for microglia; tillotson and wood 1989 astrocytes glial fibrillary acidic protein t cells t cell receptor cd3 and dendritic cells cd11c . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | fects neurons as well as glial cells and neurites before somata v spreads caudocranially from the spinal cord up to telencephalic areas and vi does not involve the activation of the apoptotic protein caspase 3. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in addition we performed immunohistochemical stainings of active caspase 3. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | we did not find evidence for the expression of casp3act in any animal suggesting that either caspase 3 is not involved in cell death and consequently that apoptosis is not a major cell death mechanism in the sod1 g93a transgenics. |
| 6152 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | integrin alpha x | 1.0 | the integrin alpha x subunit cd11c is a known marker for dendritic cells dc metlay et al. 1990 and antibodies against this protein have been widely used to analyze the distribution of dendritic cells in nervous system pa |
| 11782 | TH | tyrosine hydroxylase | tyrosine 3 monooxygenase | 1.0 | tyrosine 3 monooxygenase|superoxide dismutase 1|superoxide dismutase| |