Concurrent Equine Degenerative Myeloencephalopathy and Equine Motor Neuron Disease in Three Young Horses.
Ontology highlight
ABSTRACT:
SUBMITTER: Finno CJ
PROVIDER: S-EPMC5089576 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:A pigment retinopathy has been reported in adult horses with equine motor neuron disease (EMND) arising from chronic ?-tocopherol (?-TP) deficiency. A pigment retinopathy has not been identified in horses with neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) that affects genetically susceptible young horses with ?-TP deficiency. The objective of this report is to describe, for the first time, a pigment retinopathy in a family of ?-TP-deficient Warmbloods (WB) with clinically apparent NAD/EDM or EMND.Twenty-five WB horses from one farm underwent complete neurologic and ophthalmic examinations and serum ?-TP concentrations were assessed. Two of the most severely ataxic horses were euthanized and postmortem examinations performed.Alpha-TP deficiency was widespread on this farm (22 of 25 horses). Eleven of 25 horses were clinically normal (age range 2-12 years), one had signs of EMND (6 years of age), 10 had signs of ataxia consistent with NAD/EDM (1-10 years), and two of these were postmortem confirmed concurrent NAD/EDM and EMND. A pigment retinopathy characterized by varying amounts of granular dark pigment in the tapetal retina was observed in four clinically apparent NAD/EDM horses (two postmortem confirmed concurrent NAD/EDM and EMND) and one horse with clinical signs of EMND.A pigment retinopathy can be present in young ?-TP-deficient Warmblood horses with clinical signs of EMND as well as those with signs of NAD/EDM.
| S-EPMC5292316 | biostudies-literature
Project description:Equine degenerative myeloencephalopathy (EDM) is characterized by a symmetric general proprioceptive ataxia in young horses, and is likely underdiagnosed for 2 reasons: first, clinical signs overlap those of cervical vertebral compressive myelopathy; second, histologic lesions--including axonal spheroids in specific tracts of the somatosensory and motor systems--may be subtle. The purpose of this study was (1) to utilize immunohistochemical (IHC) markers to trace axons in the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts in healthy horses and (2) to determine the IHC staining characteristics of the neurons and degenerated axons along the somatosensory tracts in EDM-affected horses. Examination of brain, spinal cord, and nerves was performed on 2 age-matched control horses, 3 EDM-affected horses, and 2 age-matched disease-control horses via IHC for calbindin, vesicular glutamate transporter 2, parvalbumin, calretinin, glutamic acid decarboxylase, and glial fibrillary acidic protein. Primary afferent axons of the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts were successfully traced with calretinin. Calretinin-positive cell bodies were identified in a subset of neurons in the dorsal root ganglia, suggesting that calretinin IHC could be used to trace axonal projections from these cell bodies. Calretinin-immunoreactive spheroids were present in EDM-affected horses within the nuclei cuneatus medialis, cuneatus lateralis, and thoracicus. Neurons within those nuclei were calretinin negative. Cell bodies of degenerated axons in EDM-affected horses are likely located in the dorsal root ganglia. These findings support the role of sensory axonal degeneration in the pathogenesis of EDM and provide a method to highlight tracts with axonal spheroids to aid in the diagnosis of this neurodegenerative disease.
| S-EPMC4831571 | biostudies-literature
Project description:Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurologic disease that has been reported in young horses from a wide range of breeds. The disease is inherited and associated with vitamin E deficiency during the first two years of life, resulting in bilateral symmetric ataxia. A missense mutation (chr3:71,917,591 C > T) within adhesion G protein-coupled receptor L3 (ADGRL3) was recently associated with risk for EDM in the Caspian breed. In order to confirm these findings, genotyping of this missense mutation, along with the three other associated single nucleotide polymorphisms (SNPs) in the genomic region, was carried out on 31 postmortem-confirmed eNAD/EDM cases and 43 clinically phenotyped controls from various breeds. No significant association was found between eNAD/EDM confirmed cases and genotype at any of the four identified SNPs (P > 0.05), including the nonsynonymous variant (EquCab2.0 chr3:71,917,591; allelic P = 0.85). These findings suggest that the four SNPs, including the missense variant in the ADGRL3 region, are not associated with risk for eNAD/EDM across multiple breeds of horses.
| S-EPMC6770705 | biostudies-literature
Project description:Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.
| S-EPMC7995974 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) are potential biomarkers for equine sarcoids (ES).ObjectivesTo assess eca-miR-331, eca-miR-100, and eca-miR-1 as serum biomarkers for ES disease.AnimalsSixty-eight ES cases (56 horses, 12 donkeys), 69 tumor-free controls (60 horses, 9 donkeys), and 20 horses with other skin tumors.MethodsFor this case-control study, expression of serum eca-miR-331, eca-miR-100, and eca-miR-1 in ES-affected equids was compared to tumor-free age-, sex-, and breed-matched control horses and donkeys with other skin tumors using reverse transcription quantitative PCR (polymerase chain reaction) for relative miRNA quantification. Biological, preanalytical, and clinical variable influences on miRNA expression were examined. Receiver operator characteristic (ROC) curve analyses were used to determine differences in miRNA expression between groups.ResultsThe expression of eca-miR-100 was affected by age (P = .003) and expression of eca-miR-100 and eca-miR-1 were affected by hemolysis (both P < .001). Eca-miR-331 was unaffected by biological variation, hemolysis, ES type, and disease severity. Eca-miR-331 concentrations were higher in ES-affected compared to tumor-free controls (P = .002). The ROC curve analysis indicated an area under the curve of 0.65 (P = .002) with a sensitivity of 60%, specificity of 71%, and positive and negative likelihood ratios of 2.1 and 0.56, respectively, to diagnose ES. Eca-miR-331 expression did not discriminate between horses with ES and other skin tumors. Expression of eca-miR-100 and eca-miR-1 was not different between groups.Conclusions and clinical importanceSerum eca-miR-331 expression is neither sensitive nor specific enough as a single ES biomarker. If combined with other miRNAs, it may be helpful for ES diagnosis.
| S-EPMC7848377 | biostudies-literature
Project description:Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC) II and p63, low in MHC I and positive for Ki67, collagen type II (Col II) and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP) as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced) MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment.
| S-EPMC3896436 | biostudies-literature
Project description:Recumbency is a prerequisite for horses achieving rapid eye movement (REM) sleep and completing a full sleep cycle. An inability to lie down due to environmental insecurities or pain results in REM sleep deficiency, which can cause substantial impairment of welfare and health. Therefore, the present study used wearable automated sensor technology on 83 horses housed in an animal sanctuary to measure and compare the recumbency, locomotion, and standing time budgets of geriatric horses with and without chronic lameness to younger adult sound and lame horses. Recumbency times ranged from 0 to 319 min per day with an overall mean of 67.4 (±61.9) minutes; the time budget for locomotion was 19.1% (±11.2% s.d.) and for standing 75.6% (±13.1 s.d.). Interestingly, neither age nor lameness due to chronic orthopedic disease had a significant influence on recumbency times in this study. Eight horses showed symptoms of REM deficit. These horses had significantly shorter lying times (7.99 ± 11.4 min) and smaller locomotion time budgets than the other horses enrolled in this study (73.8 ± 61.8 min), indicating a general compromise of well-being. Thus, wearable sensor technology can be used to identify horses with low recumbency times at risk for REM sleep deficiency and to assess and monitor equine welfare objectively.
| S-EPMC8614510 | biostudies-literature
Project description:BackgroundThe role of the gastric microbiome in development or persistence of equine glandular gastric disease (EGGD) remains to be investigated.Hypothesis/objectivesThe objective was to characterize the glandular mucosal and gastric fluid microbiomes of horses with and without EGGD. It was hypothesized that differences in the mucosal microbiome are associated with EGGD.AnimalsTwenty-four horses were enrolled.MethodsGastroscopy was performed and EGGD scores recorded (score 0, n = 6; score 1, n = 8; score ≥2, n = 10). Gastric fluid and pinch biopsies of healthy glandular mucosa and EGGD lesions were collected via gastroscope. 16S rRNA amplicon sequencing of the gastric fluid and glandular mucosal biopsies was performed. Relationships between gastric fluid and mucosal microbial community composition were evaluated among EGGD score groups (EGGD 0-BX, EGGD 1-BX, EGGD ≥2-BX) and among endoscopic appearances: controls from horses without EGGD and normal areas, hyperemic areas, and lesions from horses with EGGD.ResultsMicrobial community structure of mucosal biopsies differed among EGGD score groups (Jaccard similarity index; P = .009). Principal coordinate analysis showed separate clusters for EGGD 0-BX and EGGD ≥2-BX.Conclusions and clinical importanceA modest difference was detected in the community structure of the gastric glandular mucosal microbiome in association with EGGD score.
| S-EPMC8478018 | biostudies-literature
Project description:Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. Generally, it's characterized by of adrenal insufficiency in consequence of adrenocorticotropic hormone (ACTH) resistance, besides of achalasia, and alacrimia. Neurologic features are varied and have been the subject of several case reports and reviews. A few cases of Allgrove syndrome with motor neuron disease have been already described. A 25-year-old white man, at the age of four, presented slowly progressive distal amyotrophy and weakness, autonomic dysfunction, dysphagia and lack of tears. He suffered later of orthostatic hypotension and erectile dysfunction. He presented distal amytrophy in four limbs, tongue myofasiculations, alacrimia, hoarseness and dysphagia due to achalasia. The ENMG showed generalized denervation with normal conduction velocities. Genetic testing revealed 2 known pathogenic variants in the AAAS gene (c.938T>C and c.1144_1147delTCTG). Our case presented a distal spinal amyotrophy with slow evolution and symptoms and signs of AS with a mutation in AAAS gen. Some cases of motor neuron disease, as ours, may be due to AAS. Early diagnosis is extremely important for symptomatic treatment.
| S-EPMC6050446 | biostudies-literature
Project description:Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and ? motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament-binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.
| S-EPMC6008238 | biostudies-literature