Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann ce... more Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using an in vitro slice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro. Immunohistochemistry for the detection of p75 NTR , CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75 NTR were substantiated by the use of in situ hybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi-to multipolar p75 NTR-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely positive for GAP-43, a marker for non-myelinating Schwann cells. The number of p75 NTR positive glia did not correlate with GFAP expression, but showed a strong correlation with a remarkable spontaneous response of CD107b positive phagocytic microglia/macrophages. Moreover, aldynoglial p75 NTR immunoreactivity negatively correlated to neuronal p75 NTR expression, which was lost during culturing. The present results demonstrate that the cultivation of organotypic murine brain slices is accompanied by a spontaneous response of both microglia/macrophages and p75 NTR positive cells, suggestive of Schwann cell like aldynoglia. The findings highlights the role of microglia/macrophages, which seem to be an important triggering factor, facilitating the occurrence of this unique type of macroglia.
<p>Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A... more <p>Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of the Central Nervous System by Kathrin Becker, Armend Cana, Wolfgang Baumgärtner, and Ingo Spitzbarth in Veterinary Pathology</p
American foulbrood (AFB) is one of the most devastating infectious diseases of honey bees with a ... more American foulbrood (AFB) is one of the most devastating infectious diseases of honey bees with a worldwide distribution. Based on clinical symptoms of AFB, the disease has been thought to have long...
Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-E... more Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of the Central Nervous System by Kathrin Becker, Armend Cana, Wolfgang Baumgärtner, and Ingo Spitzbarth in Veterinary Pathology
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2020
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016 . A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-va...
P75 neurotrophin receptor (NTR) plays a pivotal role in various tissues including the central ner... more P75 neurotrophin receptor (NTR) plays a pivotal role in various tissues including the central nervous system (CNS). Through binding its ligands, it exerts versatile functions, implicated in both neurodegeneration and regenerative events. Besides various categories of stem cells, it is considered as a prototype marker of Schwann cell-like brain glia, a unique type of macroglia, which has been referred to as aldynoglia. In fact, in the peripheral nervous system (PNS) all Schwann cell lineages express p75NTR with the exception of mature myelinating Schwann cells. Failure of remyelination is the major drawback in many neurodegenerative pathologies of the CNS, although various animal models suggest substantial endogenous glial reponses implied in neuroregeneration and remyelination, respectively. Interestingly, recent reports suggest that centrally derived Schwann cells may significantly contribute to regenerative events following CNS injury, especially under conditions of astrocytic los...
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2019
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016. A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-value <0.0001. Increasing sero-prevalence observed in goats up to 4 years old with a sharp drop in goats older than four years highlights the need for further investigation based on clinical impact and genotype characterization. While retained sero-positive sheep in the population beyond 4 years old may suggest mild clinical impact of small ruminant lentiviral infections in Kosovo sheep.
Periodic acid-Schiff (PAS)-positive granular deposits in the hippocampus have been reported previ... more Periodic acid-Schiff (PAS)-positive granular deposits in the hippocampus have been reported previously in certain inbred mouse strains such as C57BL/6 and the senescent-accelerated mouse prone-8. Here, we report for the first time that similar PAS-positive granules age dependently occur in SJL/J mice, a mouse strain, for instance, used for central nervous system disease research. Moreover, similar granules stained intensely positive with a polyclonal antibody directed against p75 neurotrophin receptor (p75(NTR)). Granular deposits were absent in young mice and developed with aging in CA1 and CA2 regions of the hippocampus. Interestingly, granules significantly diminished in SJL/J mice previously treated with cuprizone, a copper chelator, which is a useful model for toxic demyelination. The presented data support the idea that granules might be the result of an imbalance of redox-active metals and/or a dysregulation of complementary mechanisms that regulate their homeostasis in astro...
Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann ce... more Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using an in vitro slice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro. Immunohistochemistry for the detection of p75(NTR), CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75(NTR) were substantiated by the use of in situ hybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi- to multipolar p75(NTR)-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely ...
In this study, we report the first outbreak of highly pathogenic avian influenza (HPAI) A H5N8, c... more In this study, we report the first outbreak of highly pathogenic avian influenza (HPAI) A H5N8, clade 2.3.4.4b in Kosovo on 19 May 2021. The outbreak consisted of three phases: May–June 2021, September–November 2021, and January–May 2022. In total, 32 backyards and 10 commercial holdings tested positive for the virus. Interestingly, the third and last phase of the outbreak coincided with the massive H5N1 clade 2.3.4.4b epidemic in Europe. Phylogenetic analyses of 28 viral strains from Kosovo revealed that they were closely related to the H5N8 clade 2.3.4.4.b viruses that had been circulating in Albania, Bulgaria, Croatia, Hungary, and Russia in early 2021. Whole genome sequencing of the 25 and partial sequencing of three H5N8 viruses from Kosovo showed high nucleotide identity, forming a distinctive cluster and suggesting a single introduction. The results of the network analysis were in accordance with the three epidemic waves and suggested that the viral diffusion could have been ...
The low-affinity nerve growth factor receptor p75NTR is a major neurotrophin receptor involved in... more The low-affinity nerve growth factor receptor p75NTR is a major neurotrophin receptor involved in manifold and pleiotropic functions in the developing and adult central nervous system (CNS). Although known for decades, its entire functions are far from being fully elucidated. Depending on the complex interactions with other receptors and on the cellular context, p75NTR is capable of performing contradictory tasks such as mediating cell death as well as cell survival. In parallel, as a prototype marker for certain differentiation stages of Schwann cells and related CNS aldynoglial cells, p75NTR has recently gained increasing notice as a marker for cells with proposed regenerative potential in CNS diseases, such as demyelinating disease and traumatic CNS injury. Besides its pivotal role as a marker for transplantation candidate cells, recent studies in canine neuroinflammatory CNS conditions also highlight a spontaneous endogenous occurrence of p75NTR-positive glia, which potentially ...
Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a va... more 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
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2019
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016. A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-value <0.0001. Increasing sero-prevalence observed in goats up to 4 years old with a sharp drop in goats older than four years highlights the need for further investigation based on clinical impact and genotype characterization. While retained sero-positive sheep in the population beyond 4 years old may suggest mild clinical impact of small ruminant lentiviral infections in Kosovo sheep.
Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann ce... more Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using an in vitro slice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro. Immunohistochemistry for the detection of p75 NTR , CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75 NTR were substantiated by the use of in situ hybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi-to multipolar p75 NTR-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely positive for GAP-43, a marker for non-myelinating Schwann cells. The number of p75 NTR positive glia did not correlate with GFAP expression, but showed a strong correlation with a remarkable spontaneous response of CD107b positive phagocytic microglia/macrophages. Moreover, aldynoglial p75 NTR immunoreactivity negatively correlated to neuronal p75 NTR expression, which was lost during culturing. The present results demonstrate that the cultivation of organotypic murine brain slices is accompanied by a spontaneous response of both microglia/macrophages and p75 NTR positive cells, suggestive of Schwann cell like aldynoglia. The findings highlights the role of microglia/macrophages, which seem to be an important triggering factor, facilitating the occurrence of this unique type of macroglia.
<p>Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A... more <p>Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of the Central Nervous System by Kathrin Becker, Armend Cana, Wolfgang Baumgärtner, and Ingo Spitzbarth in Veterinary Pathology</p
American foulbrood (AFB) is one of the most devastating infectious diseases of honey bees with a ... more American foulbrood (AFB) is one of the most devastating infectious diseases of honey bees with a worldwide distribution. Based on clinical symptoms of AFB, the disease has been thought to have long...
Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-E... more Supplemental Material, DS1_VET_10.1177_0300985818781930 for p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of the Central Nervous System by Kathrin Becker, Armend Cana, Wolfgang Baumgärtner, and Ingo Spitzbarth in Veterinary Pathology
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2020
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016 . A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-va...
P75 neurotrophin receptor (NTR) plays a pivotal role in various tissues including the central ner... more P75 neurotrophin receptor (NTR) plays a pivotal role in various tissues including the central nervous system (CNS). Through binding its ligands, it exerts versatile functions, implicated in both neurodegeneration and regenerative events. Besides various categories of stem cells, it is considered as a prototype marker of Schwann cell-like brain glia, a unique type of macroglia, which has been referred to as aldynoglia. In fact, in the peripheral nervous system (PNS) all Schwann cell lineages express p75NTR with the exception of mature myelinating Schwann cells. Failure of remyelination is the major drawback in many neurodegenerative pathologies of the CNS, although various animal models suggest substantial endogenous glial reponses implied in neuroregeneration and remyelination, respectively. Interestingly, recent reports suggest that centrally derived Schwann cells may significantly contribute to regenerative events following CNS injury, especially under conditions of astrocytic los...
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2019
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016. A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-value <0.0001. Increasing sero-prevalence observed in goats up to 4 years old with a sharp drop in goats older than four years highlights the need for further investigation based on clinical impact and genotype characterization. While retained sero-positive sheep in the population beyond 4 years old may suggest mild clinical impact of small ruminant lentiviral infections in Kosovo sheep.
Periodic acid-Schiff (PAS)-positive granular deposits in the hippocampus have been reported previ... more Periodic acid-Schiff (PAS)-positive granular deposits in the hippocampus have been reported previously in certain inbred mouse strains such as C57BL/6 and the senescent-accelerated mouse prone-8. Here, we report for the first time that similar PAS-positive granules age dependently occur in SJL/J mice, a mouse strain, for instance, used for central nervous system disease research. Moreover, similar granules stained intensely positive with a polyclonal antibody directed against p75 neurotrophin receptor (p75(NTR)). Granular deposits were absent in young mice and developed with aging in CA1 and CA2 regions of the hippocampus. Interestingly, granules significantly diminished in SJL/J mice previously treated with cuprizone, a copper chelator, which is a useful model for toxic demyelination. The presented data support the idea that granules might be the result of an imbalance of redox-active metals and/or a dysregulation of complementary mechanisms that regulate their homeostasis in astro...
Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann ce... more Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using an in vitro slice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 days in vitro. Immunohistochemistry for the detection of p75(NTR), CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75(NTR) were substantiated by the use of in situ hybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi- to multipolar p75(NTR)-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely ...
In this study, we report the first outbreak of highly pathogenic avian influenza (HPAI) A H5N8, c... more In this study, we report the first outbreak of highly pathogenic avian influenza (HPAI) A H5N8, clade 2.3.4.4b in Kosovo on 19 May 2021. The outbreak consisted of three phases: May–June 2021, September–November 2021, and January–May 2022. In total, 32 backyards and 10 commercial holdings tested positive for the virus. Interestingly, the third and last phase of the outbreak coincided with the massive H5N1 clade 2.3.4.4b epidemic in Europe. Phylogenetic analyses of 28 viral strains from Kosovo revealed that they were closely related to the H5N8 clade 2.3.4.4.b viruses that had been circulating in Albania, Bulgaria, Croatia, Hungary, and Russia in early 2021. Whole genome sequencing of the 25 and partial sequencing of three H5N8 viruses from Kosovo showed high nucleotide identity, forming a distinctive cluster and suggesting a single introduction. The results of the network analysis were in accordance with the three epidemic waves and suggested that the viral diffusion could have been ...
The low-affinity nerve growth factor receptor p75NTR is a major neurotrophin receptor involved in... more The low-affinity nerve growth factor receptor p75NTR is a major neurotrophin receptor involved in manifold and pleiotropic functions in the developing and adult central nervous system (CNS). Although known for decades, its entire functions are far from being fully elucidated. Depending on the complex interactions with other receptors and on the cellular context, p75NTR is capable of performing contradictory tasks such as mediating cell death as well as cell survival. In parallel, as a prototype marker for certain differentiation stages of Schwann cells and related CNS aldynoglial cells, p75NTR has recently gained increasing notice as a marker for cells with proposed regenerative potential in CNS diseases, such as demyelinating disease and traumatic CNS injury. Besides its pivotal role as a marker for transplantation candidate cells, recent studies in canine neuroinflammatory CNS conditions also highlight a spontaneous endogenous occurrence of p75NTR-positive glia, which potentially ...
Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a va... more 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
Kafkas Universitesi Veteriner Fakultesi Dergisi, 2019
The objectives of this cross-sectional study were to detect the presence of small ruminant lentiv... more The objectives of this cross-sectional study were to detect the presence of small ruminant lentiviral infections in Kosovo and estimate the serological prevalence for the year of 2016. A total of 5.272 sheep and 435 goats were tested using a commercially available indirect enzymelinked immunosorbent assay (ELISA) for Maedi-Visna/Caprine Arthritis-Encephalitis, giving an overall individual sero-prevalence in sheep of 34.8% (95% confidence interval 31.8% to 38.0%), and a flock prevalence of 85%, and in goats an overall individual sero-prevalence of 15.6% (95% confidence interval 7.2% to 25.6%) and flock prevalence of 35%. Sero-prevalence in sheep was higher in the South and West of Kosovo, whereas in goats was higher in the East and South. There were no statistically significant differences in sero-prevalence between sheep in different age groups <2 year to ≥4 year. There were statistically significant differences between the age groups in goats: chi square 25.74 (3d.f.) with P-value <0.0001. Increasing sero-prevalence observed in goats up to 4 years old with a sharp drop in goats older than four years highlights the need for further investigation based on clinical impact and genotype characterization. While retained sero-positive sheep in the population beyond 4 years old may suggest mild clinical impact of small ruminant lentiviral infections in Kosovo sheep.
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