Onset of Accumulation of PrPresin Murine ME7 Scrapie in Relation to Pathological and PrP Immunohistochemical Changes

Jeffrey, Martin; Martin, Stuart; Barr, J.; Chong, Angela; Fraser, James E.

doi:10.1053/jcpa.2000.0423

Cited by 53 publications

(49 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased punctate staining was observed in the thalamus from 70 days p.i. ; thereafter, the pattern of PrP staining in both the hippocampus and the thalamus was consistent with previous reports (Jeffrey et al, 2000(Jeffrey et al, , 2001. To assess glial cell activation, astrocytes were identified using a rabbit anticow GFAP (glial fibrillary acidic protein) antibody (Dako) and microglia using the monoclonal antibodies FA11 (anti-CD68), F4/80 (both obtained from Serotec) and TIB122 (anti-leukocyte common antigen), the hybridoma for which was obtained from ECC.…”

supporting

confidence: 83%

“…To determine any relationship between cytokine expression and neuropathological events, we have determined the temporal course of the expression of a large number of cytokines in the brains of C57BLxVM/Dk mice infected with the ME7 strain of scrapie. This (ME7/CV) model was chosen as it is well characterized; the timing and nature of neuronal pathology in the hippocampus has been described in detail (Jeffrey et al, 2000(Jeffrey et al, , 2001Johnston et al, 1998). The temporal and spatial aspects of glial cell activation have received less attention in this model and are also described here.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease

Brown

Webb

Rebus

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

The temporal course of cerebral cytokine gene expression was investigated in the ME7/CV murine scrapie model to determine any association with neuropathological events. Analysis by RNase protection assay (RPA) demonstrated no transcripts for ILs 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, IFN-c or lymphotoxin-a at any time during the course of this disease. Transcripts for transforming growth factor-b1 were constitutively expressed in both control and scrapie-infected brain and were elevated at terminal disease. RPA and quantitative real-time RT-PCR detected low levels of transcripts for IL-1a, IL-1b and TNFa in scrapie-infected brain but only IL-1b was elevated consistently in all mice studied. Although glial cell activation within the hippocampus was evident from 100 days post-infection (p.i.), elevated IL-1b transcripts (and immunoreactivity) were evident from 180 days p.i., around the time of hippocampal pyramidal neuron loss, and increased steadily thereafter to reach a 3?5-fold increase at terminal disease. Even at their maximum, levels of these transcripts were disproportionately low relative to the degree of glial cell activation. It is concluded that cytokine gene expression in the ME7 scrapie-infected mouse brain, relative to the degree of reactive gliosis, is highly restricted, temporally late and disproportionately low.

show abstract

supporting

confidence: 83%

mentioning

confidence: 99%

Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease

Brown

Webb

Rebus

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…26,27,28 Electron microscopy revealed the well-described ultrastructural hallmarks of the pathology in prion diseased brain 29 and these were present in all ME7-animals from 12 weeks p.i. onwards.…”

Section: Resultsmentioning

confidence: 92%

Degenerating Synaptic Boutons in Prion Disease

Šišková

Page

O’Connor

et al. 2009

The American Journal of Pathology

View full text Add to dashboard Cite

A growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the hippocampus underpins the first behavioral changes and that there is a selective loss of presynaptic elements. The microglia have an activated morphology at this stage but they have an anti-inflammatory phenotype. We reasoned that the microglia might be involved in synaptic stripping, removing synapses undergoing a degenerative process, and that this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density revealed a progressive loss from 12 weeks post disease initiation. The loss of synapses was not associated with microglia processes; instead, we found that the postsynaptic density of the dendritic spine was progressively wrapped around the degenerating presynaptic element with loss of subcellular components. Three-dimensional reconstructions of these structures from Dual Beam electron microscopy support the conclusion that the synaptic loss in prion disease is a neuron autonomous event facilitated without direct involvement of glial cells. Previous studies described synapse engulfment by developing and injured neurons, and we suggest that this mechanism may contribute to developmental and pathological changes in synapse numbers.

show abstract

“…In addition, synaptic disorganization and loss have been described in sporadic and inherited Creutzfeldt-Jakob disease, including cases associated with octapeptide insertions (31). Accumulation of abnormal PrP at presynaptic and postsynaptic sites has been found to precede neuronal dysfunction and death and be associated with loss of synaptic contacts in the CNS of scrapie-infected mice and patients with CreutzfeldtJakob disease (29,(32)(33)(34).…”

Section: Synaptic Dysfunction In Prion and Other Neurodegenerative DImentioning

confidence: 99%

Baxdeletion prevents neuronal loss but not neurological symptoms in a transgenic model of inherited prion disease

Chiesa

Piccardo

Dossena

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transgenic Tg(PG14) mice express a mutant prion protein containing 14 octapeptide repeats, whose human homologue is associated with an inherited prion dementia. These mice develop a progressive neurological disorder characterized by ataxia and cerebellar atrophy, with massive apoptotic degeneration of granule neurons. Bax, a proapoptotic gene of the Bcl-2 family, plays a key role in regulating cell death in the nervous system. To analyze the role of Bax in the Tg(PG14) phenotype, we crossed Tg(PG14) mice with Bax ؊/؊ mice to obtain Tg(PG14)͞Bax ؊/؊ offspring. Bax deletion effectively rescued cerebellar granule neurons from apoptosis, implying that these cells die via a Bax-dependent process. Surprisingly, however, the age at which symptoms began and the duration of the clinical phase of the illness were not altered in Tg(PG14)͞ Bax ؊/؊ mice. In addition, Bax deletion failed to prevent shrinkage of the molecular layer of the cerebellum and loss of synaptophysinpositive synaptic endings. Our analysis indicates that synaptic loss makes a critical contribution to the Tg(PG14) phenotype. These results provide insights into the pathogenesis of prion diseases and have important implications for the treatment of these disorders.synapse ͉ apoptosis ͉ neurodegeneration ͉ cerebellum

show abstract

Onset of Accumulation of PrPresin Murine ME7 Scrapie in Relation to Pathological and PrP Immunohistochemical Changes

Cited by 53 publications

References 23 publications

Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease

Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease

Degenerating Synaptic Boutons in Prion Disease

Baxdeletion prevents neuronal loss but not neurological symptoms in a transgenic model of inherited prion disease

Contact Info

Product

Resources

About