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Measurement of 8-hydroxy-2′-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia.
Abstract: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. Objective: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses. Methods: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. Methods: Case-control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA) utilized. Concentration of 8-OHdG was quantitated in both CSF and serum and compared between groups. Results: No correlation was established between the measures of 8-OHdG in serum and CSF and group. CSF median [8-OHdG] for NAD/DM was 169.9 pg/mL (IQR : 67.18-210.6), CVSM 157.1 pg/mL (IQR : 132.1-229.1), EPM 131.4 pg/mL (IQR : 102.1-193.2), and control 149.8 pg/mL (IQR : 113.3-196.4). Serum median [8-OHdG] for NAD/DM was 130 pg/mL (IQR : 51.73-157.2), CVSM 125.8 pg/mL (IQR : 62.8-170.8), EPM 120.6 pg/mL (IQR : 87.23-229.7), and control 157.6 pg/mL (IQR : 97.15-245.6). Poisson regression analysis showed no difference established once confounding variables were considered. Conclusions: Eight-OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.
© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2024-01-11 PubMed ID: 38205913PubMed Central: PMC10937501DOI: 10.1111/jvim.16988Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study investigated whether levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, differ in serum and cerebrospinal fluid (CSF) among horses with neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) compared to other neurological diseases and healthy controls.
- The researchers found no significant differences in 8-OHdG levels between groups, suggesting it may not be useful for diagnosing NAD/DM in horses before death.
Background
- 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a biomarker commonly used to measure oxidative damage to DNA.
- Oxidative stress has been implicated in various neurodegenerative diseases in humans and animal models.
- Neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) is a neurodegenerative disease in horses that leads to proprioceptive ataxia (difficulty with body coordination and limb placement).
- Currently, antemortem diagnosis of NAD/DM is challenging, and there is interest in identifying biomarkers like 8-OHdG to aid diagnosis.
Hypotheses
- 8-OHdG levels in CSF and serum would be higher in horses with NAD/DM compared to horses with other neurologic diseases and neurologically normal control horses.
- 8-OHdG levels would be higher in CSF compared to serum within the NAD/DM group, reflecting localized oxidative damage.
Methods
- Study Design: Case-control study using biobanked samples.
- Subjects: Fifty client-owned horses divided into four groups based on postmortem diagnoses:
- 20 horses with NAD/DM
- 10 horses with cervical vertebral compressive myelopathy (CVSM)
- 10 horses with equine protozoal myeloencephalitis (EPM)
- 10 neurologically normal controls
- Sample Collection: Serum and cerebrospinal fluid samples collected between November 2010 and March 2022.
- Measurement: Quantification of 8-OHdG concentrations in CSF and serum using a commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA).
- Statistical Analysis: Comparison of 8-OHdG levels between groups using Poisson regression analysis controlling for confounding variables.
Results
- Median 8-OHdG concentrations in CSF (pg/mL, interquartile range (IQR)):
- NAD/DM: 169.9 (67.18 – 210.6)
- CVSM: 157.1 (132.1 – 229.1)
- EPM: 131.4 (102.1 – 193.2)
- Control: 149.8 (113.3 – 196.4)
- Median 8-OHdG concentrations in serum (pg/mL, IQR):
- NAD/DM: 130 (51.73 – 157.2)
- CVSM: 125.8 (62.8 – 170.8)
- EPM: 120.6 (87.23 – 229.7)
- Control: 157.6 (97.15 – 245.6)
- No significant correlation was found between 8-OHdG concentrations in either serum or CSF and disease groups after adjusting for confounding factors.
- Contrary to initial hypothesis, 8-OHdG levels were not significantly higher in CSF compared to serum in NAD/DM horses.
Conclusions
- 8-OHdG concentrations measured in serum and CSF did not distinguish horses with NAD/DM from those with other neurological diseases or controls.
- This suggests that oxidative DNA damage, as measured by 8-OHdG, is not markedly increased in horses with NAD/DM at the time of diagnosis.
- Therefore, 8-OHdG may not be a useful biomarker for antemortem diagnosis of NAD/DM in horses.
- The lack of elevated oxidative stress markers indicates that oxidative damage is likely not ongoing or not detectable in body fluids during the clinical phase of NAD/DM.
Implications and Future Directions
- Since 8-OHdG does not differentiate NAD/DM horses, alternative biomarkers or diagnostic techniques are needed for early and accurate diagnosis.
- Further research may focus on different oxidative stress markers or explore other pathological mechanisms involved in equine neurodegenerative diseases.
- Longitudinal studies could help determine if oxidative stress markers change earlier in disease progression before clinical signs are apparent.
Cite This Article
APA
Palmisano M, Kulp J, Bender S, Stefanovski D, Robinson M, Johnson A.
(2024).
Measurement of 8-hydroxy-2′-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia.
J Vet Intern Med, 38(2), 1207-1213.
https://doi.org/10.1111/jvim.16988 Publication
Researcher Affiliations
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
- Department of Pathobiology, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA.
MeSH Terms
- Humans
- Animals
- Horses
- 8-Hydroxy-2'-Deoxyguanosine
- Neurodegenerative Diseases / veterinary
- Case-Control Studies
- NAD
- Horse Diseases / diagnosis
- Neuroaxonal Dystrophies / veterinary
- Ataxia / veterinary
Grant Funding
- 1-400666-xxxx-2000-5919 / Firestone/Tamworth/Raker-Tulleners Grant
Conflict of Interest Statement
Authors declare no conflict of interest.
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Citations
This article has been cited 1 times.- Șerban M, Toader C, Covache-Busuioc RA. The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration. Int J Mol Sci 2025 Aug 3;26(15).
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