Differential expression of neuropsin and protease M/neurosin in oligodendrocytes after injury to the spinal cord

Terayama, Ryuji; Bandô, Yoshio; Takahashi, Takayuki; Yoshida, Shigetaka

doi:10.1002/glia.20058

Cited by 41 publications

(57 citation statements)

References 49 publications

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“…Consistent with previous studies, the expression of neuropsin mRNA in WT mice was increased in the white matter of the spinal cord after injury (Tomizawa et al, 1999;Terayama et al, 2004). Extending on previous results, our findings demonstrate that neuropsin may promote oligodendrocyte death, demyelination and axonal degeneration after SCI.…”

Section: Discussionsupporting

confidence: 92%

“…These proteases are expressed by neurons, astrocytes, microglia or inflammatory cells, whereas neuropsin is expressed exclusively by oligodendrocytes (Terayama et al, 2004). Thus, it is likely that neuropsin functions to modify the extracellular environment with these proteases after injury.…”

Section: Discussionmentioning

confidence: 99%

“…The method used for in situ hybridization was described in previous papers (Yoshida et al, 1994;Chen et al, 1998;Terayama et al, 2004). In brief, slide-mounted sections were postfixed in 4% formaldehyde in 0.1 M PB, and treated with 10 µg/ml of proteinase K, followed by 0.25% acetic anhydrate in 0.1 M triethanolamine (pH 8.0) for 10 min at RT.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…The sections were dehydrated and defatted in graded alcohol solutions and chloroform, respectively and air-dried before application of the hybridization buffer at 55 ˚C for 1 hr. Hybridization was performed overnight at 55 ˚C in a humidified chamber with hybridization buffer containing 10 ng/100 µl of the DIG-labeled cRNA probe (Terayama et al, 2004). The hybridized sections were washed in 4× standard saline citrate (SSC) buffer (pH 7.4) for 20 min and then in 50% formamide/4× SSC buffer at 60 ˚C for 30 min.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…Our previous experiments showed that traumatic, excitotoxic and immunological injury induced expression of neuropsin mRNA in the area surrounding the lesion in the CNS (Tomizawa et al, 1999;Terayama et al, 2004;Terayama et al, 2005a). Combined in situ hybridization and immunohistochemistry revealed that most of the cells expressing neuropsin mRNA were mature oligodendrocytes (Terayama et al, 2004).…”

Section: Introductionmentioning

confidence: 97%

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Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

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Abbreviations: SCI, spinal cord injury; DIG, digoxigenin; APC, adenomatus polyposis coli; MBP, myelin basic protein; TUNEL, TdT-mediated dUTP-fluorescein nick end labeling -3 - AbstractPrevious studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the central nervous system (CNS). The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin -/-) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin -/-mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI.Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin -/-mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin -/-mice compared to WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.-4 -

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: In Situ Hybridizationmentioning

confidence: 99%

Section: In Situ Hybridizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

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Involvement of neuropsin in the pathogenesis of experimental autoimmune encephalomyelitis

Terayama

Bandô

Yamada

et al. 2005

Glia

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Inflammation, demyelination, and axonal damage of the central nervous system (CNS) are major pathological features of multiple sclerosis (MS). Proteolytic digestion of the blood-brain barrier and myelin protein by serine proteases is known to contribute to the development and progression of MS. Neuropsin, a serine protease, has a role in neuronal plasticity, and its expression has been shown to be upregulated in response to injury to the CNS. To determine the possible involvement of neuropsin in demyelinating diseases of the CNS, we examined its expression in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a recognized animal model for MS. Neuropsin mRNA expression was induced in the spinal cord white matter of mice with EAE. Combined in situ hybridization and immunohistochemistry demonstrated that most of the cells expressing neuropsin mRNA showed immunoreactivity for CNPase, a cell-specific marker for oligodendrocytes. Mice lacking neuropsin (neuropsin-/-) exhibited an altered EAE progression characterized by delayed onset and progression of clinical symptoms as compared to wild-type mice. Neuropsin-/- mice also showed attenuated demyelination and delayed oligodendroglial death early during the course of EAE. These observations suggest that neuropsin is involved in the pathogenesis of EAE mediated by demyelination and oligodendroglial death.

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Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis

Bandô

Hagiwara²,

Suzuki

et al. 2017

Glia

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of the disease. Here, we examined the pathophysiological role of Kallikrein 6 (Klk6), a serine protease produced by oligodendrocytes (OLs), in EAE using Klk6 knockout (Klk6-/-) mice. Compared with Klk6+/+ (wild-type) mice, Klk6-/- mice showed milder EAE symptoms, including delayed onset and milder paralysis. Loss of Klk6 suppressed matrix metalloprotease-9 expression and diminished the infiltration of peripheral inflammatory cells into the CNS by decreasing blood-brain barrier (BBB) permeability and reducing expression levels of inflammatory cytokines, chemokines and their receptors. Scanning electron microscopic analysis revealed demyelination characterized by myelin detachment from the axons in the early phase of EAE progression (days 3-7) in Klk6+/+ mice but not in Klk6-/- mice. Interestingly, anti-MOG (myelin oligodendrocyte glycoprotein) autoantibody was also detected in the cerebrospinal fluid (CSF) and spinal cord on day 3 after MOG immunization. Furthermore, treatment of primary cultured OLs with anti-MOG autoantibody induced oligodendroglial morphological changes and increases in myelin basic protein and Klk6 expression. We also developed a novel enzyme-linked immunoabsorbent assay method for detecting activated KLK6 in human CSF. In human autopsy brain samples, expression of active KLK6 was detected in OLs using an antibody that specifically recognizes the protein's activated form. Taken together, our findings demonstrate that Klk6 secreted by OLs plays a critical role in the pathogenesis of EAE/MS and that it might serve as a potential therapeutic target for MS.

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Differential expression of neuropsin and protease M/neurosin in oligodendrocytes after injury to the spinal cord

Cited by 41 publications

References 49 publications

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Involvement of neuropsin in the pathogenesis of experimental autoimmune encephalomyelitis

Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis

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