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 play a role in Schwann cell–mediated CNS remyelination. The aim of the present communication is to review the pleiotropic functions of p75NTR in the CNS with a special emphasis on its role as an immunohistochemical marker in neuropathology. Following a brief illustration of the expression of p75NTR in neurogenesis and in developed neuronal populations, the implications of p75NTR expression in astrocytes, oligodendrocytes, and microglia are addressed. A special focus is put on the role of p75NTR as a cell marker for specific differentiation stages of Schwann cells and a regeneration-promoting CNS population, collectively referred to as aldynoglia.
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.
In recent years, honey bee colony losses in the Republic of Kosovo remained largely unknown. From 2019 to 2021, 81 apiaries with different disease suspicions were investigated in the framework of ...honey bee disease passive surveillance. Fifty-nine of the eighty-one apiaries were tested for Vairimorpha ceranae, Vairimorpha apis, trypanosomatids Lotmaria passim, and Crithidia mellificae. All samples were positive for V. ceranae (100%) whereas L. passim was found with a lower frequency (11.9%). V. apis and C. mellificae were not found. Thirteen of the eighty-one apiaries were tested for seven viruses (ABPV, CBPV, DWV, BQCV, SBV, IAPV, KBV) and five of them were found (ABPV, CBPV, DWV, BQCV, SBV). The most frequently detected viruses in honey bees and Varroa mites were DWV (100%) followed by BQCV, ABPV, SBV, and CBPV (92.3%, 69.2%, 30.8%, and 7.7%, respectively). Varroa mite samples had different degrees of co-infection by viruses. Nine of the eighty-one apiaries consisted of brood combs with larvae, eight of them were AFB positive, ERIC I genotype, and one EFB positive. This paper represents the first molecular investigation (PCR) and detection of the honey bee viruses ABPV, CBPV, DWV, BQCV, and SBV as well as V. ceranae, L. passim, and M. plutonius in the Republic of Kosovo.
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 caused by secondary spreads among farms and/or different introductions of the same virus from wild birds. The persistent circulation of the same virus over a one-year period highlights the potential risk of the virus becoming endemic, especially in settings with non-adequate biosecurity.
A cross-sectional survey was conducted in Kosovo to determine the presence and prevalence of bovine leukemia virus antibodies in cattle. A total of 5,051 serum samples from 315 villages were ...collected during 2016. Samples were tested using commercial indirect enzyme-linked immunosorbent assay. At least one sero-positive animal was found in 55 (17.5%) of the villages sampled, of which 23 had more than one sero-positive detected. Overall individual sero-prevalence, corrected for geographic distribution of samples, was found to be 2.26% (95% c.i. 1.62% to 3.04%). There were no statistically significant associations between serological status and herd size or age of animal, although sero-prevalence in 5-year-old cattle was higher than in the other ages. There was a statistical significant heterogeneity in sero-prevalence between different geographic zones of Kosovo (chi-square value = 20.68 (4 d.f.); (p=0.0004). Pairwise comparisons showed that sero-prevalence in the south was significantly higher than in the east and in the north and sero-prevalence in the west was significantly higher than in the north. The 3.11% aggregated sero-prevalence for the two highest sero-prevalence zones, south and west, was significantly higher than the 1.57% aggregated sero-prevalence for the remaining zones, centre, east and north (Fisher exact p-value (2-tail) = 0.0004). The reason for higher prevalence in the south and west of Kosovo is uncertain. These results may serve to enrich the information of bovine leukemia virus distribution in the region, as well as a starting point for the future control and eradication strategy in Kosovo.
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.
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 ...existed in the Republic of Kosovo honey bee colonies. This passive surveillance study was intended to confirm the presence and determine the distribution of AFB in the Republic of Kosovo, based on the examination of clinical symptoms, rapid immunochromatographic tests, and microbiological and molecular identification of the etiological agent Paenibacillus larvae. From 2007 until 2019, official veterinary inspectors collected 2027 brood combs from a total of 373 apiaries clinically suspected as an AFB outbreak. Samples were collected in 26 out of 38 municipalities of the country predominantly during spring and autumn. P. larvae were isolated from 219 out of 373 apiaries, i.e., 58.71%. All samples with AFB clinical symptoms of the disease were positive in the immunochromatographic test. The presence of the AFB was demonstrated in 24 municipalities. Seventeen positive apiaries from different regions were randomly selected in the years 2016 to 2018 in order to characterize the isolates circulating most recently by ERIC genotyping. The presence of both ERIC I and II genotypes, as well as of a biotype with a profile slightly different from ERIC I and II, was observed. The results indicate a need for a change in approach in future control strategies and training programs for early diagnosis and improved management of apicultural practices.
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 (p75NTR). 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 astrocyte–neuron coupling, respectively. It remains to be determined whether the unsuspected immunoreactivity for p75NTR represents a false-positive reaction or whether p75NTR is crucially involved in the pathogenesis of age-related hippocampal granular deposits in mice.
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