Variations on brain microglial gene expression of MMPs, RECK, and TIMPs in inflammatory and non-inflammatory diseases in dogs

Stein, Veronika M.; Puff, Christina; Genini, Sem; Contioso, Vanessa Bono; Baumgärtner, Wolfgang; Tipold, Andrea

doi:10.1016/j.vetimm.2011.06.029

Cited by 12 publications

(13 citation statements)

References 38 publications

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“…Reverse transcription was performed using 1 μg RNA in 1 × reverse transcriptase reaction (RT) buffer with 0.5 mM of each deoxynucleotide triphosphate (dNTP), 10 μM random hexamers (Promega), 0.5 U/μL RNAse inhibitor (RNAse Out, Invitrogen) and 0.2 U/μL Omniscript Reverse Transcriptase (Qiagen) in a total volume of 20 μL at 37°C for 1 hour. For the generation of standard dilution series qualitative PCR was performed with cDNA from DH82 cells using primers specific for the housekeeping genes glyceraldehyde 3‐phosphate dehydrogenase (GAPDH), hypoxanthine‐guanine phosphoribosyltransferase (HPRT), and elongation factor (EF)‐1α, and for MMP‐2 and MMP‐9, respectively (Table ; ). Qualitative PCR was performed using a PTC200 thermocycler (Biozym Diagnostic, Hessisch–Oldendorf, Germany) under the conditions as described .…”

Section: Methodsmentioning

confidence: 99%

Spatio‐Temporal Development of Axonopathy in Canine Intervertebral Disc Disease as a Translational Large Animal Model for Nonexperimental Spinal Cord Injury

et al. 2012

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Spinal cord injury (SCI) represents a devastating central nervous system disease that still lacks sufficient therapies. Here, dogs are increasingly recognized as a preclinical animal model for the development of future therapies. The aim of this study was a detailed characterization of axonopathy in canine intervertebral disc disease, which produces a mixed contusive and compressive injury and functions as a spontaneous translational animal model for human SCI. The results revealed an early occurrence of ultrastructurally distinct axonal swelling. Immunohistochemically, enhanced axonal expression of β-amyloid precursor protein, non-phosphorylated neurofilament (n-NF) and growth-associated protein-43 was detected in the epicenter during acute canine SCI. Indicative of a progressive axonopathy, these changes showed a cranial and caudally accentuated spatial progression in the subacute disease phase. In canine spinal cord slice cultures, immunoreactivity of axons was confined to n-NF. Real-time quantitative polymerase chain reaction of naturally traumatized tissue and slice cultures revealed a temporally distinct dysregulation of the matrix metalloproteinases (MMP)-2 and MMP-9 with a dominating expression of the latter. Contrasting to early axonopathy, diminished myelin basic protein immunoreactivity and phagocytosis were delayed. The results present a basis for assessing new therapies in the canine animal model for translational research that might allow partial extrapolation to human SCI.

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Section: Methodsmentioning

confidence: 99%

Spatio‐Temporal Development of Axonopathy in Canine Intervertebral Disc Disease as a Translational Large Animal Model for Nonexperimental Spinal Cord Injury

et al. 2012

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“…37,39,46 Despite advances in the understanding of microglia in the healthy dog, it remains unclear as to whether these cells respond to various disease states stereotypically or if they adapt their responses to the underlying pathologic conditions. 47 In many canine diseases, microglial markers are upregulated to varying degrees and the cells show enhanced phagocytosis. 48,49 …”

Section: T-cell Responsesmentioning

confidence: 99%

Perspectives on Meningoencephalomyelitis of Unknown Origin

Coates

Jeffery

2014

Veterinary Clinics of North America: Small Animal Practice

102

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“…In this respect, a number of recent studies have highlighted MMPs and their inhibitors as additional crucial proteins in the molecular pathogenesis of nervous distemper [61,62,63]. …”

Section: Canine Distemper Leukoencephalitis — Novel Aspects Of Itsmentioning

confidence: 99%

“…Substantiating these cells as an important source, microglia isolated from dogs with inflammatory CNS diseases, including CDV-DL, contain a higher number of MMP-9 mRNA transcripts compared to microglia from dogs suffering from non-inflammatory CNS diseases. This might account for a facilitated invasion of white blood cells into the CNS [63]. However, a canine macrophage/monocyte cell line (DH82 cells) persistently infected with CDV, displays only minimal variations in the number of MMP-9 mRNA transcripts compared to non-infected DH82 cells [62].…”

Section: Canine Distemper Leukoencephalitis — Novel Aspects Of Itsmentioning

confidence: 99%

New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

Lempp

Spitzbarth

Puff

et al. 2014

Viruses

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Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes, expression of vimentin is generally restricted to immature or reactive astrocytes. Thus, vimentin-positive astrocytes might constitute an important cell population for CDV persistence and spread, as well as lesion progression. In vitro models, such as dissociated glial cell cultures, as well as organotypic brain slice cultures have contributed to a better insight into mechanisms of infection and certain morphological and molecular aspects of CDV-DL. Summarized, recent in vivo and in vitro studies revealed remarkable new aspects of nervous distemper. These new perceptions substantially improved our understanding of the pathogenesis of CDV-DL and might represent new starting points to develop novel treatment strategies.

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Variations on brain microglial gene expression of MMPs, RECK, and TIMPs in inflammatory and non-inflammatory diseases in dogs

Cited by 12 publications

References 38 publications

Spatio‐Temporal Development of Axonopathy in Canine Intervertebral Disc Disease as a Translational Large Animal Model for Nonexperimental Spinal Cord Injury

Spatio‐Temporal Development of Axonopathy in Canine Intervertebral Disc Disease as a Translational Large Animal Model for Nonexperimental Spinal Cord Injury

Perspectives on Meningoencephalomyelitis of Unknown Origin

New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

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