Differential expression of TAR DNA-binding protein (TDP-43) in the central nervous system of horses afflicted with equine motor neuron disease (EMND): a preliminary study of a potential pathologic marker.
Abstract: Equine motor neuron disease (EMND) is a neurodegenerative disorder of unknown etiology affecting horses worldwide. Trans-Active Response DNA Binding Protein of 43 kDa (TDP-43) has been reported in the central nervous system (CNS) of several neurodegenerative conditions in humans including Amyotrophic Lateral Sclerosis (ALS) and assumed to play role in the disease. We examined whether horses afflicted with EMND express the TDP-43 in CNS. Ten horses with EMND and 6 controls of different ages and breed we enrolled. Detection of presence of TDP-43 protein in the CNS was analyzed by immunohistochemical staining using rabbit anti-human TARDBP (TDP-43) polyclonal antibody. Formalin fixed neuronal tissues from medulla, cervical, and lumbar spinal cord were harvested from EMND and from control horses. Sections were assigned randomly to TDP-43 treated or rabbit anti-IgG as control. Nuclear staining of TDP-43 was detected in one of the neural tissues of 75 % of EMND-positive and 0 of 0 % of control horses in the central nervous system (medulla, and/or cervical spinal cord and/or lumbar spinal cord). TDP-43 antibody was detected in the nucleus of EMND horses and no cytoplasmic staining was noted. As in ALS, there was no pattern of age clustering associated with the detection of TDP-43. This is the first report on the staining of TDP-43 in neuronal tissues of horses and suggests that TDP-43 may play a role in the pathogenesis of EMND. Further studies are needed to elucidate the etiologic role of this protein in the diseases.
Publication Date: 2012-08-24 PubMed ID: 22918699DOI: 10.1007/s11259-012-9533-yGoogle 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
- Research Support
- N.I.H.
- Extramural
- Cells
- Clinical Pathology
- Clinical Study
- Comparative Study
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Equine Motor Neuron Disease
- Genetics
- Horses
- Immunohistochemistry
- Laboratory Methods
- Nervous System
- Neurological Diseases
- Neurology
- Pathogenesis
- Protein
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores the presence and potential role of a protein, TDP-43, in horses affected by a neurodegenerative disorder known as equine motor neuron disease (EMND). The researchers discovered that TDP-43 was found more frequently in the central nervous system (CNS) of horses with EMND compared to healthy horses.
Introduction
- The study mainly revolved around equine motor neuron disease (EMND), a neurodegenerative illness that affects horses globally but whose causes are unknown.
- TDP-43, the protein under investigation, has been previously observed in the CNS of humans affected by neurodegenerative conditions, including Amyotrophic Lateral Sclerosis (ALS).
- The researchers hypothesized that if TDP-43 is also present in horses with EMND, it may play a possible role in the advancement of the disease.
Methods
- The study enlisted ten horses diagnosed with EMND and six healthy horses of different ages and breeds as controls.
- The investigators used an immunohistochemical staining technique with a special antibody to detect the presence of the TDP-43 protein in the CNS.
- Neuronal tissues from the medulla, cervical, and lumbar spinal cord were collected from both EMND-diagnosed and control horses.
- The specimens were randomly assigned to be treated with TDP-43 or a control solution.
Findings
- The researchers observed TDP-43 in the nuclei of neural tissues in 75% of horses with EMND, but not in any of the healthy control horses.
- The TDP-43 antibody was identified in the nucleus of neurons in EMND horses, with no cytoplasmic staining observed.
- Unlike ALS, the researchers did not find any association between the detection of TDP-43 and the age of the horses.
Conclusions
- This is the first study reporting the staining of TDP-43 in neuronal tissues of horses, indicating that this protein might play a role in the development of EMND in horses.
- Future studies are needed to better understand the function of this protein in the disease process, which can possibly direct toward breakthroughs in its diagnosis, prevention, or treatment.
Cite This Article
APA
El-Assaad I, Di Bari JA, Yasuda K, Divers TJ, Summers BA, de Lahunta A, Mohammed H.
(2012).
Differential expression of TAR DNA-binding protein (TDP-43) in the central nervous system of horses afflicted with equine motor neuron disease (EMND): a preliminary study of a potential pathologic marker.
Vet Res Commun, 36(4), 221-226.
https://doi.org/10.1007/s11259-012-9533-y Publication
Researcher Affiliations
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, S1 070 Schurman Hall, Ithaca, NY 14853, USA.
MeSH Terms
- Animals
- Antibodies, Anti-Idiotypic / metabolism
- Biomarkers / metabolism
- DNA-Binding Proteins / metabolism
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Medulla Oblongata / metabolism
- Medulla Oblongata / pathology
- Motor Neuron Disease / metabolism
- Motor Neuron Disease / pathology
- Motor Neuron Disease / veterinary
- Rabbits
- Retrospective Studies
- Spinal Cord / metabolism
- Spinal Cord / pathology
Grant Funding
- IR29NS2967-01AL / NINDS NIH HHS
References
This article includes 23 references
- Bodansky A, Kim JM, Tempest L, Velagapudi A, Libby R, Ravits J. TDP-43 and ubiquitinated cytoplasmic aggregates in sporadic ALS are low frequency and widely distributed in the lower motor neuron columns independent of disease spread.. Amyotroph Lateral Scler 2010 May 3;11(3):321-7.
- Feki M, Souissi M, Mebazaa A. [Vitamin E: structure, metabolism, and functions].. Ann Med Interne (Paris) 2001 Oct;152(6):384-91.
- Divers TJ, Mohammed HO, Cummings JF, Valentine BA, De Lahunta A, Jackson CA, Summers BA. Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease.. Equine Vet J 1994 Sep;26(5):409-15.
- Valentine BA, de Lahunta A, George C, Summers BA, Cummings JF, Divers TJ, Mohammed HO. Acquired equine motor neuron disease.. Vet Pathol 1994 Jan;31(1):130-8.
- Pamphlett R, Kum Jew S. TDP-43 inclusions do not protect motor neurons from sporadic ALS.. Acta Neuropathol 2008 Aug;116(2):221-2.
- Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43.. Cell 2009 Mar 20;136(6):1001-4.
- Turner BJ, Bäumer D, Parkinson NJ, Scaber J, Ansorge O, Talbot K. TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy.. BMC Neurosci 2008 Oct 28;9:104.
- Yamanaka K, Boillee S, Roberts EA, Garcia ML, McAlonis-Downes M, Mikse OR, Cleveland DW, Goldstein LS. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice.. Proc Natl Acad Sci U S A 2008 May 27;105(21):7594-9.
- Igaz LM, Kwong LK, Lee EB, Chen-Plotkin A, Swanson E, Unger T, Malunda J, Xu Y, Winton MJ, Trojanowski JQ, Lee VM. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice.. J Clin Invest 2011 Feb;121(2):726-38.
- Divers TJ, Cummings JE, de Lahunta A, Hintz HF, Mohammed HO. Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron.. Am J Vet Res 2006 Jan;67(1):120-6.
- Mohammed HO, Divers TJ, Summers BA, de Lahunta A. Vitamin E deficiency and risk of equine motor neuron disease.. Acta Vet Scand 2007 Jul 2;49(1):17.
- Wang IF, Wu LS, Shen CK. TDP-43: an emerging new player in neurodegenerative diseases.. Trends Mol Med 2008 Nov;14(11):479-85.
- Wilson AC, Dugger BN, Dickson DW, Wang DS. TDP-43 in aging and Alzheimer's disease - a review.. Int J Clin Exp Pathol 2011 Jan 30;4(2):147-55.
- Ascherio A, Weisskopf MG, O'reilly EJ, Jacobs EJ, McCullough ML, Calle EE, Cudkowicz M, Thun MJ. Vitamin E intake and risk of amyotrophic lateral sclerosis.. Ann Neurol 2005 Jan;57(1):104-10.
- Gurney ME, Cutting FB, Zhai P, Doble A, Taylor CP, Andrus PK, Hall ED. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis.. Ann Neurol 1996 Feb;39(2):147-57.
- Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model.. Nat Neurosci 2007 May;10(5):608-14.
- Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.. Science 2008 Mar 21;319(5870):1668-72.
- Cummings JF, de Lahunta A, George C, Fuhrer L, Valentine BA, Cooper BJ, Summers BA, Huxtable CR, Mohammed HO. Equine motor neuron disease; a preliminary report.. Cornell Vet 1990 Oct;80(4):357-79.
- Weber Polack E, King JM, Cummings JF, de Lahunta A, Divers TJ, Mohammed HO. Quantitative assessment of motor neuron loss in equine motor neuron disease (EMND).. Equine Vet J 1998 May;30(3):256-9.
- Deng HX, Zhai H, Bigio EH, Yan J, Fecto F, Ajroud K, Mishra M, Ajroud-Driss S, Heller S, Sufit R, Siddique N, Mugnaini E, Siddique T. FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis.. Ann Neurol 2010 Jun;67(6):739-48.
- Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boillée S, Rule M, McMahon AP, Doucette W, Siwek D, Ferrante RJ, Brown RH Jr, Julien JP, Goldstein LS, Cleveland DW. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice.. Science 2003 Oct 3;302(5642):113-7.
- Winton MJ, Igaz LM, Wong MM, Kwong LK, Trojanowski JQ, Lee VM. Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution, sequestration, and aggregate formation.. J Biol Chem 2008 May 9;283(19):13302-9.
- Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.. Science 2006 Oct 6;314(5796):130-3.
Citations
This article has been cited 2 times.- Prpar Mihevc S, Majdič G. Canine Cognitive Dysfunction and Alzheimer's Disease - Two Facets of the Same Disease?. Front Neurosci 2019;13:604.
- Sasaki N, Imamura Y, Sekiya A, Itoh M, Furuoka H. Four cases of equine motor neuron disease in Japan.. J Equine Sci 2016;27(3):119-124.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
