title: Quantitative assessment of hsp70, IL-1β and TNF-α in the spinal cord of dogs with E40K SOD1-associated degenerative myelopathy.
abstract: Inflammation is involved in the pathogenesis of many neurodegenerative diseases. Canine degenerative myelopathy (DM) is a progressive adult-onset neurodegenerative disease commonly associated with an E40K missense mutation in the SOD1 gene. DM has many similarities to some familial forms of human amyotrophic lateral sclerosis (ALS) and may serve as an important disease model for therapy development. Pro-inflammatory mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and heat shock protein (hsp) 70 play a role in the pathogenesis of ALS. The focus of the current work was to determine whether an inflammatory phenotype is present in canine DM as defined by IL-1β, TNF-α, and hsp70 responses in cerebrospinal fluid (CSF) and spinal cord tissue. Concentrations of hsp70, IL-1β and TNF-α were below the limits of detection by ELISA in the CSF of both normal and DM-affected dogs. Immunohistochemical staining for hsp70 was significantly increased in ependymal cells lining the spinal cord central canal of DM-affected dogs (P = 0.003). This was not associated with increased IL-1β or TNF-α staining, but was associated with increased CD18 staining in the gray matter of DM-affected dogs. These results suggest that hsp70 in spinal cord tissue is a potential inflammatory signature in canine DM.
authors.affiliation: MedVet Medical and Cancer Center for Pets, 300 E. Wilson Bridge Rd, Worthington, OH 43085, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Lovett
authors.affiliation: Department of Veterinary Medicine & Surgery, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Coates
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 207 Goss Laboratory, 1925 Coffey Rd., Columbus, OH 43210, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 207 Goss Laboratory, 1925 Coffey Rd., Columbus, OH 43210, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Oglesbee
authors.affiliation: MedVet Medical and Cancer Center for Pets, 300 E. Wilson Bridge Rd, Worthington, OH 43085, USA.
authors.forename: W
authors.initials: W
authors.lastname: Fenner
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, 601 Vernon L. Tharp St, Columbus, OH 43210, USA. Electronic address: moore.2204@osu.edu.
authors.forename: S A
authors.initials: SA
authors.lastname: Moore
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism*; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007150:Immunohistochemistry / Q000662:veterinary; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013118:Spinal Cord Diseases / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D018821:CD18 Antigens; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; C000606290:SOD1 protein, human; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis (ALS); Canine; Heat shock protein 70 (hsp70); Neuroinflammation; Superoxide dismutase-1 (SOD-1)