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Altered microglia function contributes to loss of CNS homeostasis during aging in the brain. Few studies have evaluated age-related alterations in spinal cord microglia. We previously demonstrated that lumbar spinal cord microglial expression of inducible nitric oxide synthase (iNOS) was equivalent between aging, neurologically normal dogs and dogs with canine degenerative myelopathy (Toedebusch et al. 2018, Mol Cell Neurosci. 88, 148-157). This unexpected finding suggested that microglia in aging spinal cord have a pro-inflammatory polarization. In this study, we reexamined our microglial results (Toedebusch et al. 2018, Mol Cell Neurosci. 88, 148-157) within the context of aging rather than disease by comparing microglia in aging versus young adult dogs. For both aging and young adult dogs, the density of microglia was significantly higher closest to the motor neuron cell body. However, there was no difference in densities between aging versus young adult dogs at all distances except for the furthest distance analyzed. The number of motor neurons with polarized microglia was higher in aging dogs; yet, the density per motor neuron of arginase-1-expressing microglia was reduced in aging dogs compared with young adult dogs. Finally, aging dogs had increased steady-state mRNA levels for genes consistent with activated microglia compared with young adult dogs. However, altered mRNA levels were limited to the lumbar spinal cord. These data suggested that aging dog spinal cord microglia exhibit regional immunophenotypic differences, which may render lumbar motor neurons more susceptible to age-related pathological insults.

Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman.

Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer‐reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers provide a crucial information in the progress of neurodegenerative diseases with a minimally invasive sampling method. Validated blood-based biomarker application in people with amyotrophic lateral sclerosis would derive numerous benefits. Canine degenerative myelopathy is a naturally occurring animal disease model to study the biology of human amyotrophic lateral sclerosis. Serum derived exosomes are potential carriers for cell-specific cargoes making them ideal venue to study biomarkers for a variety of diseases and biological processes. This study assessed the exosomal proteins that may be assigned as surrogate biomarker that may reflect biochemical changes in the central nervous system. Exosomes were isolated from canine serum using commercial exosome isolation reagents. Exosomes target proteins contents were analyzed by the Western blotting method. The profiles of potential biomarker candidates in spinal cord homogenate and that of serum-derived exosomes were found elevated in dogs with degenerative myelopathy as compared to control subjects. Serum-derived exosomal biomolecules can serve as surrogate biomarkers in neurodegenerative diseases. A canine with degenerative myelopathy can serve as a model animal to study human amyotrophic lateral sclerosis. Serum-derived exosomes contain Transactive Response DNA Binding Protein 43 (TDP-43), a potential biomarker candidate. The levels of spinal cord TDP-43 proteins and that of serum-derived exosomes exhibited similar profiling. Therefore, serum derived exosomes may be used as a venue for establishing blood-based biomarkers for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]