Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis

Klemens, Johanna; Ciurkiewicz, Małgorzata; Chludzinski, Elisa; Iseringhausen, M.; Klotz, D.; Pfankuche, Vanessa Maria; Ulrich, Reiner; Herder, Vanessa; Puff, Christina; Baumgärtner, Wolfgang; Beineke, Andreas

doi:10.1038/s41598-019-48146-9

Cited by 18 publications

(15 citation statements)

References 111 publications

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“…Acyl-CoA synthetase produces acyl-CoA for numerous metabolic pathways, such as cellular lipid metabolism; transcriptional regulation; intracellular protein transportation; and protein acylation in various tissues, including skeletal muscle, the liver, and the brain 13 . ACSL5 is a neurotoxic A1 astrocyte-related gene, and is up-regulated in A1 astrocytes 14 . A1 astrocytes are abundant in various neurodegenerative diseases, including ALS, and they induce the death of neurons in the central nervous system 15 .…”

Section: Discussionmentioning

confidence: 99%

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.

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Section: Discussionmentioning

confidence: 99%

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

et al. 2020

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“…PRCoV replicates predominantly in the lungs and is mostly detected in the lower respiratory tract [ 21 ]. First, we applied immunofluorescence microscopy to visualize the expression of pAPN and used ImageJ to quantify the amount of expression of pAPN on wdPTECs and wdPBECs.…”

Section: Resultsmentioning

confidence: 99%

“…To localize the expression of pAPN, IHC staining of porcine tissue and PTECs was applied [ 21 ]. Briefly, the samples were fixed with 3% paraformaldehyde (PFA) in PBS for 1 h. Samples were washed with phosphate-buffered saline containing 5% skim milk and embedded in paraffin blocks for sectioning.…”

Section: Methodsmentioning

confidence: 99%

The Cell Tropism of Porcine Respiratory Coronavirus for Airway Epithelial Cells Is Determined by the Expression of Porcine Aminopeptidase N

Peng

Punyadarsaniya

Shin

et al. 2020

Viruses

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Porcine respiratory coronavirus (PRCoV) infects the epithelial cells in the respiratory tract of pigs, causing a mild respiratory disease. We applied air–liquid interface (ALI) cultures of well-differentiated porcine airway cells to mimic the respiratory tract epithelium in vitro and use it for analyzing the infection by PRCoV. As reported for most coronaviruses, virus entry and virus release occurred mainly via the apical membrane domain. A novel finding was that PRCoV preferentially targets non-ciliated and among them the non-mucus-producing cells. Aminopeptidase N (APN), the cellular receptor for PRCoV was also more abundantly expressed on this type of cell suggesting that APN is a determinant of the cell tropism. Interestingly, differentiation-dependent differences were found both in the expression of pAPN and the susceptibility to PRCoV infection. Cells in an early differentiation stage express higher levels of pAPN and are more susceptible to infection by PRCoV than are well-differentiated cells. A difference in the susceptibility to infection was also detected when tracheal and bronchial cells were compared. The increased susceptibility to infection of bronchial epithelial cells was, however, not due to an increased abundance of APN on the cell surface. Our data reveal a complex pattern of infection in porcine differentiated airway epithelial cells that could not be elucidated with immortalized cell lines. The results are expected to have relevance also for the analysis of other respiratory viruses.

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“…This is the first study to confirm the expression and distribution of AQP4 using immunohistochemistry in normal canine brains. Previous veterinary publications have exclusively investigated the presence of CNS AQP4 immunohistochemistry in pathological conditions [ 11 , 12 ], but no information was available so far in non-pathological canine brains. This finding supports the assumption that AQP4 plays also in the normal canine brains a crucial role in maintaining water homeostasis, cell migration and neuroexcitation [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

“…Only scarce information is available about AQP4 distribution in diseased canine brains. Klemens et al [ 11 ] described the expression of AQP4 in canine cerebellar samples of canine distemper virus infected dogs. This study showed that there was a more severe loss of AQP4 in acute distemper lesions when compared to subacute or chronic lesions in these dogs.…”

Section: Introductionmentioning

confidence: 99%

Aquaporin-4 protein expression in normal canine brains

et al. 2021

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Background Aquaporin-4 (AQP4) is in growing recognition as potential marker for cancer progression, differentiation and therapeutic intervention. No information is available about AQP4 expression in the normal canine brain. The aim of this histopathological study is to confirm the presence of AQP4 by immunohistochemistry technique in a group of non-pathological canine brains and to describe its expression and distribution across the brain. Results Twelve non-pathological canine brains of various ages (ranging from 21 days to 17 years) and breeds were included in the study. Immunohistochemical expression of AQP4 was analyzed using formalin-fixed paraffin-embedded brain tissue sections. The findings were correlated between AQP4 expressing cells and astrocytes using glial fibrillary acidic protein (GFAP). AQP4 expression was more marked in the astrocyte foot processes of subpial, perivascular and periventricular surfaces in all specimens. The majority of the canine brain sections (9/12) presented with an AQP4 predilection for white matter tracts. Interestingly, the two youngest dogs (21 days and 3 months old) were characterized by diffuse AQP4 labelling in both grey and white matter tracts. This result may suggest that brain development and ageing may play a role in the AQP4 distribution throughout the canine brain. Conclusions This is the first study to describe immunohistochemical distribution of AQP4 in normal canine brains. The AQP4 expression and distribution in non-pathological canine brains was comparable to other species. Larger studies are needed to substantiate the influence of breed and ageing on AQP4 expression in the normal canine brain.

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Neurotoxic potential of reactive astrocytes in canine distemper demyelinating leukoencephalitis

Cited by 18 publications

References 111 publications

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

The Cell Tropism of Porcine Respiratory Coronavirus for Airway Epithelial Cells Is Determined by the Expression of Porcine Aminopeptidase N

Aquaporin-4 protein expression in normal canine brains

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