Tetranectin in cerebrospinal fluid of patients with multiple sclerosis

Stoevring, Birgitte; Jaliashvili, Irakli; Thougaard, Annemette; Ensinger, Christian; Høgdall, Claus; Rasmussen, Lars S.; Sellebjerg, Finn; Christiansen, Michael

doi:10.1080/00365510600863929

Cited by 13 publications

(3 citation statements)

References 27 publications

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“…The 2 most significantly upregulated genes were subunits C and T of the troponin complex (TNNC, FC of 272, and TNNT, FC of 226), which plays a role in intra-axonal movements in rat dorsal root ganglia (43). Additional genes that were highly upregulated include myosin essential light chain (MYL3, FC of 44), which plays a role in synaptic plasticity (44), and tetranectin (CLEC3B, FC of 24), a glycoprotein that regulates proteolytic processes in neurons and dendrites (45). In addition, a number of innate immune genes were upregulated at 3 dpi (Fig.…”

Section: Resultsmentioning

confidence: 99%

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Arnold

Girke

Sureshchandra

et al. 2016

J Virol

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Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection. V aricella-zoster virus (VZV) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) (1). VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster (shingles), a painful disease that affects almost 1 million individuals in the United States alone (2). VZV is transmitted through the inhalation of virus-laden saliva droplets or by direct contact with the infectious fluid from vesicles...

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Section: Resultsmentioning

confidence: 99%

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Arnold

Girke

Sureshchandra

et al. 2016

J Virol

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“…TNA have been proved showing limited variation between individual CSF samples [Stoop et al, 2010]. A recent proteomic study reported TNA as being one of four proteins in the CSF of patients with MS that is absent in controls [Hammack et al, 2004], and soon a research using ELISA method revealed that in definite MS and patients with first attack of MS, TNA secretion did not change in the brain [Stoevring et al, 2006]. In a recent similar research, CSF TNA levels were proved increased in epileptic patients while serum‐TN levels decreased [Wang et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients

Qin

Yang

et al. 2011

J of Cellular Biochemistry

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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with complex immunopathogenesis. Using the 2-D DIGE technology, we separate CSF proteins from patients with active MS and control subjects. Three of the seven differential proteins identified were related with complement system, and the network analysis of the differential proteins revealed complement activation involvement in active MS. Complement C4b (gamma chain) was confirmed elevated by performing western blotting analysis (P < 0.01). The present results are an independent quantitative proteomic measure in CSF from active MS patients. The differential expression of the complement C4b and related proteins in CSF provides potential biomarkers as well as evidence for the involvement of complement activation in the pathogenesis of MS disease.

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“…Reduced serum TN concentration in several cancers is considered an indication of poor prognosis [14]. One proteomic study reported that TN is one of four proteins elevated in the cerebrospinal fluid (CSF) of patients with multiple sclerosis [15], although another study reported high TN concentrations (∼0.5 mg/L) in normal CSF [16]. …”

Section: Introductionmentioning

confidence: 99%

Tetranectin Knockout Mice Develop Features of Parkinson Disease

Wang

Zhang

Yao

et al. 2014

Cell Physiol Biochem

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Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs) may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD). Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN) gene (TN^-/-) and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old) TN^-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia) and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc) and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT) mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN^-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

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Tetranectin in cerebrospinal fluid of patients with multiple sclerosis

Abstract: These results indicate that TN may play a role in neurological diseases and may serve as a diagnostic aid in MS.

Cited by 13 publications

References 27 publications

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients

Tetranectin Knockout Mice Develop Features of Parkinson Disease

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