Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3<sup>−/−</sup>Mice

Riemer, Constanze; Schultz, Julia; Burwinkel, Michael; Schwarz, Anja; Mok, Simon Wing Fai; Gültner, Sandra; Bamme, Theresa; Norley, Stephen; Landeghem, Frank K.H. van; Liu, Bao; Gérard, Craig; Baier, Michael

doi:10.1128/jvi.01371-08

Cited by 41 publications

(31 citation statements)

References 76 publications

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“…The involvement of CXCL12/ CXCR4 signaling in hMSCs migration is consistent with findings in hypoglossal nerve injury (24), ischemic (63), and glioma (11) (6,45). In prion diseases, impairment of microglial migration, associated with the increased accumulation of PrP Sc but prolongation of survival, has been reported in CXCR3 gene deficient mice infected with prions (47). Microglial recruitment in retina after intraocular injection of homogenates from prion-infected neuroblastoma cells was inhibited by CCR5 antagonist, suggesting the involvement of CCR5 in microglial response to prion infection (34), although ablation of CCR5 gene did not influence the incubation period after prion infection (55).…”

Section: Discussionsupporting

confidence: 85%

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Song

Furuoka

Horiuchi

2011

J Virol

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Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions of neurodegenerative diseases; however, the precise mechanisms by which MSCs migrate remain to be elucidated. In this study, we carried out an in vitro migration assay to investigate the chemoattractive factors for MSCs in the brains of prion-infected mice. The migration of immortalized human MSCs (hMSCs) was reduced by their pretreatment with antibodies against the chemokine receptors, CCR3, CCR5, CXCR3, and CXCR4 and by pretreatment of brain extracts of prion-infected mice with antibodies against the corresponding ligands, suggesting the involvement of these receptors, and their ligands in the migration of hMSCs. In agreement with the results of an in vitro migration assay, hMSCs in the corpus callosum, which are considered to be migrating from the transplanted area toward brain lesions of prion-infected mice, expressed CCR3, CCR5, CXCR3, and CXCR4. The combined in vitro and in vivo analyses suggest that CCR3, CCR5, CXCR3, and CXCR4, and their corresponding ligands are involved in the migration of hMSCs to the brain lesions caused by prion propagation. In addition, hMSCs that had migrated to the right hippocampus of prion-infected mice expressed CCR1, CX3CR1, and CXCR4, implying the involvement of these chemokine receptors in hMSC functions after chemotactic migration. Further elucidation of the mechanisms that underlie the migration of MSCs may provide useful information regarding application of MSCs to the treatment of prion diseases.

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Section: Discussionsupporting

confidence: 85%

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Song

Furuoka

Horiuchi

2011

J Virol

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“…Our study suggests that blocking CXCR3 is beneficial and warrants further investigation of this pathway in TON as well as evaluation of the effects of a number of CXCR3 antagonists, which are in clinical development for treating inflammatory diseases in human subjects. This study, together with previous findings that deleting CXCR3 prevents retinal neuronal cell death after an acute increase in intraocular pressure, 21 prolongs survival times after prion infection, 57 reduces NMDA-induced neuronal cell death in brain, 58 and attenuates plaque formation and behavioral deficits in Alzheimer disease, 59 highlights a role of CXCR3 in neurodegenerative diseases. The CXCL10/CXCR3 axis plays a critical role in inflammation by recruiting activated T lymphocytes, monocytes, and macrophages.…”

Section: Discussionsupporting

confidence: 80%

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Liu

Zhu

et al. 2017

The American Journal of Pathology

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Traumatic optic neuropathy (TON) is an acute injury of the optic nerve secondary to trauma. Loss of retinal ganglion cells (RGCs) is a key pathological process in TON, yet mechanisms responsible for RGC death remain unclear. In a mouse model of TON, real-time noninvasive imaging revealed a dramatic increase in leukocyte rolling and adhesion in veins near the optic nerve (ON) head at 9 hours after ON injury. Although RGC dysfunction and loss were not detected at 24 hours after injury, massive leukocyte infiltration was observed in the superficial retina. These cells were identified as T cells, microglia/monocytes, and neutrophils but not B cells. CXCL10 is a chemokine that recruits leukocytes after binding to its receptor C-X-C chemokine receptor (CXCR) 3. The levels of CXCL10 and CXCR3 were markedly elevated in TON, and up-regulation of CXCL10 was mediated by STAT1/3. Deleting CXCR3 in leukocytes significantly reduced leukocyte recruitment, and prevented RGC death at 7 days after ON injury. Treatment with CXCR3 antagonist attenuated TON-induced RGC dysfunction and cell loss. In vitro co-culture of primary RGCs with leukocytes resulted in increased RGC apoptosis, which was exaggerated in the presence of CXCL10. These results indicate that leukocyte recruitment in retinal vessels near the ON head is an early event in TON and the CXCL10/CXCR3 axis has a critical role in recruiting leukocytes and inducing RGC death. (Am J Pathol 2017, 187: 352e365; http://dx

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“…Resident glial cells of the brain functionally express CXCR3, but the impact of glial CXCR3 expression on AD progression is not yet clarified (23-26). ies examining the role of CXCR3 in other models of neurodegeneration, showing the absence of CXCR3 is associated with attenuated microglial activation, reduced expression of inflammatory factors, and constrained microglial recruitment (25,26,55,58). Concerning the mechanisms leading to diminished Aβ load in CXCR3-deficient APP/PS1 mice, based on the in vivo phagocysotis data, we hypothesized that CXCR3-deficient microglia are more capable of phagocytosing Aβ in the APP/PS1 model.…”

Section: Discussionmentioning

confidence: 99%

“…CXCR3 is a well-known modulator of microglial function (23,25,26,55). To elucidate the impact of Cxcr3 -/-on the morphological phenotype of microglia in APP/ PS1 mice, we characterized periplaque accumulation and activation by morphological criteria.…”

Section: Decreased Aβ Deposition and Aβ Level In Cxcr3-deficient App/ps1mentioning

confidence: 99%

CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model

Krauthausen¹,

Kummer²,

Zimmermann³

et al. 2014

J. Clin. Invest.

119

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Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3^−/−Mice

Cited by 41 publications

References 76 publications

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model

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Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3−/−Mice

Cited by 41 publications

References 76 publications

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model

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Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3^−/−Mice