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Molecular Neurobiology Feb 2021Longevity-associated neurological disorders have been observed across human and canine aging populations. Alzheimer's disease (AD) and canine cognitive dysfunction...
Longevity-associated neurological disorders have been observed across human and canine aging populations. Alzheimer's disease (AD) and canine cognitive dysfunction syndrome (CDS) represent comparable diseases affecting both species as they age. Translational diagnostic and therapeutic research is needed for these incurable diseases. The amyloid β (Aβ) peptide family are AD-associated peptides with identical amino acid sequences between dogs and humans. Plasma Aβ42 concentration increases with age and decreases with AD in humans, and cerebrospinal fluid (CSF) concentration decreases in AD and correlates inversely with the amyloid load within the brain. Similarly, CSF Aβ42 concentrations decrease in dogs with CDS but there is limited and conflicting information on plasma Aβ42 concentrations in aging dogs and dogs with CDS. We measured plasma concentrations of Aβ42 and Aβ40 with an ultrasensitive single-molecule array assay (SIMOA) in a population of healthy aging dogs of different life stages (n = 36) and dogs affected with CDS (n = 11). In addition, the ratio of Aβ42/β40 was calculated. The mean plasma concentrations of Aβ42 and Aβ40 increased significantly with age (r = 0.27, p = 0.001; and r = 0.42, p < 0.001, respectively) and with life stage: puppy/junior group (0.43-2 years): 1.23 ± 0.95 and 38.26 ± 49.43 pg/mL; adult/mature group (2.1-9 years): 10.99 ± 5.45 and 131.05 ± 80.17 pg/mL; geriatric/senior group (9.3-14.5 years): 18.65 ± 16.65 and 192.88 ± 146.38 pg/mL, respectively. Concentrations of Aβ42 and Aβ40 in dogs with CDS (11.0-15.6 years) were significantly lower than age-matched healthy dogs at 11.61 ± 6.39 and 150.23 ± 98.2 pg/mL (p = 0.0048 and p = 0.001), respectively. Our findings suggest the dynamics of canine plasma amyloid concentrations are analogous to that found in aging humans with and without AD.
Topics: Aging; Amyloid beta-Peptides; Animals; Cognitive Dysfunction; Dogs; Female; Male; Pets
PubMed: 32970242
DOI: 10.1007/s12035-020-02140-9 -
Veterinarni Medicina Nov 2023Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The...
Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek's disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical.
PubMed: 38163046
DOI: 10.17221/75/2023-VETMED -
Microorganisms May 2022The gut microbiota plays an important role in regulating brain function, influencing psychological and emotional stability. The correlations between conspecific...
The gut microbiota plays an important role in regulating brain function, influencing psychological and emotional stability. The correlations between conspecific aggression, gut microbiota, and physiological homeostasis were further studied in inbred laying chicken lines, 63 and 72, which were diversely selected for Marek’s disease, and they also behave differently in aggression. Ten sixty-week-old hens from each line were sampled for blood, brain, and cecal content. Neurotransmitters, cytokines, corticosterone, and heterophil/lymphocyte ratios were determined. Cecal microbiota compositions were determined by bacterial 16s rRNA sequencing, and functional predictions were performed. Our data showed that the central serotonin and tryptophan levels were higher in line 63 compared to line 72 (p < 0.05). Plasma corticosterone, heterophil/lymphocyte ratios, and central norepinephrine were lower in line 63 (p < 0.05). The level of tumor necrosis factor α tended to be higher in line 63. Faecalibacterium, Oscillibacter, Butyricicoccus, and Bacteriodes were enriched in line 63 birds, while Clostridiales vadin BB60, Alistipes, Mollicutes RF39 were dominated in line 72. From the predicted bacterial functional genes, the kynurenine pathway was upregulated in line 72. These results suggested a functional linkage of the line differences in serotonergic activity, stress response, innate immunity, and gut microbiota populations.
PubMed: 35744601
DOI: 10.3390/microorganisms10061081 -
Veterinary Research Apr 2024This article reviews the avian viruses that infect the skin of domestic farm birds of primary economic importance: chicken, duck, turkey, and goose. Many avian viruses... (Review)
Review
This article reviews the avian viruses that infect the skin of domestic farm birds of primary economic importance: chicken, duck, turkey, and goose. Many avian viruses (e.g., poxviruses, herpesviruses, Influenza viruses, retroviruses) leading to pathologies infect the skin and the appendages of these birds. Some of these viruses (e.g., Marek's disease virus, avian influenza viruses) have had and/or still have a devasting impact on the poultry economy. The skin tropism of these viruses is key to the pathology and virus life cycle, in particular for virus entry, shedding, and/or transmission. In addition, for some emergent arboviruses, such as flaviviruses, the skin is often the entry gate of the virus after mosquito bites, whether or not the host develops symptoms (e.g., West Nile virus). Various avian skin models, from primary cells to three-dimensional models, are currently available to better understand virus-skin interactions (such as replication, pathogenesis, cell response, and co-infection). These models may be key to finding solutions to prevent or halt viral infection in poultry.
Topics: Animals; Poultry; Poultry Diseases; Skin; Virus Diseases
PubMed: 38671518
DOI: 10.1186/s13567-024-01310-0 -
Frontiers in Immunology 2022The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek's disease (MD) which...
The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek's disease (MD) which is caused by an oncogenic herpesvirus; Marek's disease virus (MDV). To determine differential functional abilities of T cells associated with resistance and susceptibility to MD, we identified immunodominant CD4+TCRvβ1 T cell epitopes within the pp38 antigen of MDV in B19 and B21 MHC haplotype chickens using an ELISPOT assay for chicken IFN-gamma. These novel pp38 peptides were used to characterize differential functional abilities of T cells as associated with resistance and susceptibility to MD. The results demonstrated an upregulation of cytokines (IL-2, IL-4, IL-10) and lymphocyte lysis-related genes (perforin and granzyme B) in an antigen specific manner using RT-PCR. In the MD-resistant chickens (B21 MHC haplotype), antigen-specific and non-specific response was highly skewed towards Th2 response as defined by higher levels of IL-4 expression as well as lymphocyte lysis-related genes compared to that in the MD-susceptible chicken line (B19 MHC haplotype). Using CD107a degranulation assay, the results showed that MDV infection impairs cytotoxic function of T cells regardless of their genetic background. Taken together, the data demonstrate an association between type of T cell response to pp38 and resistance to the disease and will shed light on our understanding of immune response to this oncogenic herpesvirus and failure to induce sterile immunity.
Topics: Animals; Antiviral Agents; Chickens; Cytokines; Epitopes, T-Lymphocyte; Granzymes; Herpesvirus 2, Gallid; Interleukin-10; Interleukin-2; Interleukin-4; Marek Disease; Perforin
PubMed: 36189228
DOI: 10.3389/fimmu.2022.973762 -
International Journal of Molecular... Sep 2022Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to... (Review)
Review
Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to participate in the regulation of many physiological and pathological processes in both humans and animals. One such process is viral infection in humans and animals, in which the host miRNAs-alone or in conjunction with the virus-interact on two levels: viruses may regulate the host's miRNAs to evade its immune system, while the host miRNAs can play anti- or pro-viral roles. The purpose of this comprehensive review is to present the key miRNAs involved in viral infections in humans and animals. We summarize the data in the available literature, indicating that the signature miRNAs in human viral infections mainly include 12 miRNAs (i.e., miR-155, miR-223, miR-146a, miR-122, miR-125b, miR-132, miR-34a, miR -21, miR-16, miR-181 family, let-7 family, and miR-10a), while 10 miRNAs are commonly found in animals (i.e., miR-155, miR-223, miR-146a, miR-145, miR-21, miR-15a/miR-16 cluster, miR-181 family, let-7 family, and miR-122) in this context. Knowledge of which miRNAs are involved in different viral infections and the biological functions that they play can help in understanding the pathogenesis of viral diseases, facilitating the future development of therapeutic agents for both humans and animals.
Topics: Animals; Humans; MicroRNAs; Virus Diseases; Viruses
PubMed: 36142450
DOI: 10.3390/ijms231810536 -
Veterinary Medicine (Auckland, N.Z.) 2022Marek's disease virus is a devastating infection, causing high morbidity and mortality in chickens in Ethiopia.
BACKGROUND
Marek's disease virus is a devastating infection, causing high morbidity and mortality in chickens in Ethiopia.
METHODS
The current study was conducted from March to November, 2021 with the general objective of performing antemortem and postmortem, isolation, and molecular detection of Marek's disease virus from outbreak cases in southwestern Ethiopia. Accordingly, based on outbreak information reported from the study sites namely, Bedelle, Yayo, and Bonga towns in southwestern Ethiopia, 50 sick chickens were sampled. The backyard and intensive farming systems of chickens were included in the sampling and priorities were given for chickens that showed clinical signs that are characteristics of Marek's disease.
RESULTS
By clinical examinations, paralysis of legs and wings, gray eye, loss of weight, difficulty in breathing, and depression were recorded on all chickens sampled for this study and death of diseased chickens was observed. In addition, enlargement of the spleen and gross lesions of the liver and heart were recorded during postmortem examination. The death of infected chickens was observed in both vaccinated and non-vaccinated flocks. Out of 50 pooled feather follicle samples, Marek's disease virus was isolated from 14/50 (28%) by cell culture method and out of six tissue samples, the virus was isolated from 5/6(83.30%). By Real time polymerization chain reaction technique, which was targeted to detect the Meq gene, Marek's disease virus was detected from 18/50 feather follicles which accounts for 36% of sampled chickens.
CONCLUSION
In general, current study showed that the circulating Marek's disease virus in southwestern Ethiopia was caused by the oncogenic Gallid herpesvirus-2 (Serotype-1). Further research on molecular characterization of revolving virus in current and other regions is recommended for effective control of the disease through vaccination.
PubMed: 36199365
DOI: 10.2147/VMRR.S376795 -
Annals of Neurology Sep 2020We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls... (Observational Study)
Observational Study
OBJECTIVE
We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD.
METHODS
Amyloid-β 1 to 42 (Aβ ), total tau (t-tau) and phosphorylated tau (p-tau) at the threonine 181 position were measured using the high-precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear-mixed effects models.
RESULTS
We found patients with PD had lower CSF t-tau (median = 157.7 pg/mL; range = 80.9-467.0); p-tau (median = 13.4 pg/mL; range = 8.0-40.1), and Aβ (median = 846.2 pg/mL; range = 238.8-3,707.0) than HCs at baseline (CSF t-tau median = 173.5 pg/mL; range = 82.0-580.8; p-tau median = 15.4 pg/mL; range = 8.1-73.6; and Aβ median = 926.5 pg/mL; range = 239.1-3,297.0; p < 0.05-0.001) and a moderate-to-strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50-0.97; p < 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF Aβ at baseline and these patients with PD had lower p-tau levels (median = 10.8 pg/mL; range = 8.0-32.8) compared with 27.7% of HCs with pathologically low CSF Aβ (CSF p-tau median = 12.8 pg/mL; range 8.2-73.6; p < 0.03) In longitudinal CSF analysis, we found patients with PD had greater decline in CSF Aβ (mean difference = -41.83 pg/mL; p = 0.03) and CSF p-tau (mean difference = -0.38 pg/mL; p = 0.03) at year 3 compared with HCs. Baseline CSF Aβ values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD.
INTERPRETATION
Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3-year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020;88:574-587.
Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Disease Progression; Female; Humans; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Prospective Studies; tau Proteins
PubMed: 32542885
DOI: 10.1002/ana.25811 -
PLoS Biology Mar 2020Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it...
Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it increases vaccination coverage required to prevent disease spread and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek disease virus (MDV) in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease.
Topics: Animals; Chickens; Feathers; Herpesvirus 2, Gallid; Host-Pathogen Interactions; Marek Disease; Vaccination; Viral Load; Viral Vaccines; Virulence; Virus Shedding
PubMed: 32134914
DOI: 10.1371/journal.pbio.3000619 -
Nature Communications Jan 2024Theoretical models have successfully predicted the evolution of poultry pathogen virulence in industrialized farm contexts of broiler chicken populations. Whether there...
Theoretical models have successfully predicted the evolution of poultry pathogen virulence in industrialized farm contexts of broiler chicken populations. Whether there are ecological factors specific to more traditional rural farming that affect virulence is an open question. Within non-industrialized farming networks, live bird markets are known to be hotspots of transmission, but whether they could shift selection pressures on the evolution of poultry pathogen virulence has not been addressed. Here, we revisit predictions for the evolution of virulence for viral poultry pathogens, such as Newcastle's disease virus, Marek's disease virus, and influenza virus, H5N1, using a compartmental model that represents transmission in rural markets. We show that both the higher turnover rate and higher environmental persistence in markets relative to farms could select for higher optimal virulence strategies. In contrast to theoretical results modeling industrialized poultry farms, we find that cleaning could also select for decreased virulence in the live poultry market setting. Additionally, we predict that more virulent strategies selected in markets could circulate solely within poultry located in markets. Thus, we recommend the close monitoring of markets not only as hotspots of transmission, but as potential sources of more virulent strains of poultry pathogens.
Topics: Animals; Poultry; Chickens; Influenza A Virus, H5N1 Subtype; Farms; Epidemiological Models; Influenza in Birds
PubMed: 38242897
DOI: 10.1038/s41467-024-44777-3