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Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob disease.

Llorens F, López-González I, Thüne K, Carmona M, Zafar S, Andréoletti O, Zerr I, Ferrer I - Front Aging Neurosci (2014)

Bottom Line: The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls.Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD.Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany ; Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain.

ABSTRACT
The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NFκB/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD.

No MeSH data available.


Related in: MedlinePlus

Region-specific cell signaling in sCJD MM1 mice is shown. Western blot analysis of p-STAT3, STAT3 and IκBα levels in the cerebral cortex and cerebellum of control and sCJD MM1 mice at different dpi. Densitometry values of three animals/time point are shown.
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Figure 7: Region-specific cell signaling in sCJD MM1 mice is shown. Western blot analysis of p-STAT3, STAT3 and IκBα levels in the cerebral cortex and cerebellum of control and sCJD MM1 mice at different dpi. Densitometry values of three animals/time point are shown.

Mentions: STAT3 protein expression levels were increased in the cortex of MM1 samples at clinical stages while no significant differences were observed in the cerebellum. However, increased levels of p-STAT-3 were observed at pre-clinical and clinical stages in cortex whereas minor increases were detected in the cerebellum at clinical stages (Figure 7).


Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob disease.

Llorens F, López-González I, Thüne K, Carmona M, Zafar S, Andréoletti O, Zerr I, Ferrer I - Front Aging Neurosci (2014)

Region-specific cell signaling in sCJD MM1 mice is shown. Western blot analysis of p-STAT3, STAT3 and IκBα levels in the cerebral cortex and cerebellum of control and sCJD MM1 mice at different dpi. Densitometry values of three animals/time point are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120692&req=5

Figure 7: Region-specific cell signaling in sCJD MM1 mice is shown. Western blot analysis of p-STAT3, STAT3 and IκBα levels in the cerebral cortex and cerebellum of control and sCJD MM1 mice at different dpi. Densitometry values of three animals/time point are shown.
Mentions: STAT3 protein expression levels were increased in the cortex of MM1 samples at clinical stages while no significant differences were observed in the cerebellum. However, increased levels of p-STAT-3 were observed at pre-clinical and clinical stages in cortex whereas minor increases were detected in the cerebellum at clinical stages (Figure 7).

Bottom Line: The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls.Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD.Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany ; Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain.

ABSTRACT
The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NFκB/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD.

No MeSH data available.


Related in: MedlinePlus