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1.
J Comp Pathol ; 178: 1-8, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32800101

ABSTRACT

Four cases of a rare melanotic variant of malignant nerve sheath tumour (MNST) in dogs are described. All four cases presented with neurological clinical signs due to multicentric, intradural, intra- and extraparenchymal neoplasms that surrounded the spinal and cranial nerves and infiltrated the adjacent spinal cord and brain. The dogs were young (3 months to 3 years of age), all were female and four different breeds were represented. Characteristic histological features were interweaving fascicles of spindle-shaped cells, sometimes with an architecture reminiscent of Antoni A and B patterns. Some spindle cells showed prominent cytoplasmic melanin pigmentation and such cells were positive by Masson-Fontana stain. Immunohistochemistry performed in three cases was positive for S100 and vimentin, strongly positive for melan A in the melanized cells and negative for glial fibrillary acidic protein and periaxin. Non-melanized cells did not express melan A. Transmission electron microscopy findings in one case were consistent with a peripheral nerve sheath tumour and demonstrated cytoplasmic pre-melanosomes and melanosomes. Melanotic variants of MNSTs are rare in animals with only a solitary report of two previous canine cases in the literature.


Subject(s)
Dog Diseases , Nerve Sheath Neoplasms/veterinary , Animals , Dogs , Female , Immunohistochemistry/veterinary , MART-1 Antigen/metabolism , Microscopy, Electron/veterinary , Nerve Sheath Neoplasms/pathology , Peripheral Nerves/pathology , Peripheral Nervous System Neoplasms/pathology , Peripheral Nervous System Neoplasms/veterinary , Spinal Cord/metabolism , Spinal Cord/pathology , Vimentin/metabolism
2.
J Comp Pathol ; 177: 1-4, 2020 May.
Article in English | MEDLINE | ID: mdl-32505235

ABSTRACT

An 8-year-old Anglo-European gelding with progressive neurological signs was humanely destroyed and submitted for necropsy examination. The right parietal cortex was disrupted by a well-demarcated, intraparenchymal, 1.5 cm diameter, tan, homogeneous, dense mass. Microscopical examination was consistent with an astrocytoma, which was confirmed on the basis of strong immunohistochemical labelling for glial fibrillary acidic protein. The neoplastic population lacked immunolabelling for oligodendrocyte transcription factor 2. Labelling for ionized calcium binding adaptor molecule 1 highlighted large numbers of reactive microglia throughout the proliferation and in the adjacent neuroparenchyma. While rare, primary brain tumours should be considered as a differential in horses presenting with progressive neurological signs.


Subject(s)
Astrocytoma/veterinary , Brain Neoplasms/veterinary , Horse Diseases/diagnosis , Animals , Astrocytoma/diagnosis , Astrocytoma/pathology , Autopsy/veterinary , Brain Neoplasms/diagnosis , Glial Fibrillary Acidic Protein/metabolism , Horses , Immunohistochemistry/veterinary , Male , Oligodendrocyte Transcription Factor 2/metabolism
3.
J Comp Pathol ; 160: 15-22, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29729717

ABSTRACT

The relationship between inflammatory cells and tumour biology has been defined in many human intracranial neoplasms, but it is relatively poorly characterized in veterinary medicine. The aim of this study was to define the immune cell infiltration in cases of feline glioma and its possible association with tumour morphology and type. A retrospective search identified 18 gliomas that met inclusion criteria. Tumours were subjected to immunohistochemistry (IHC) for CD3, CD20, Iba1, MAC387 and factor VIII-related antigen. For each antibody, the number of labelled cells was counted in 10 high-power (×400) fields and a cumulative score for each antibody was generated. Intratumoural and peritumoural CD3+ T lymphocytes were observed in all cases and occurred primarily within perivascular spaces and rarely around areas of necrosis or leptomeningeal spread. Perivascular CD20+ B lymphocytes were detected in 12/18 (67%) cases and occurred within and around tumours and near areas of leptomeningeal spread. MAC387 immunoreactivity highlighted intravascular monocytes in 9/18 (50%) cases, but failed to highlight tumour-associated macrophages. Intratumoural and peritumoural Iba1 immunoreactivity was observed in all cases, with increased overall intensity around areas of necrosis and leptomeningeal spread. Intratumoural and peritumoural factor VIII-related antigen immunoreactivity was also detected in all cases and was concentrated in areas of microvascular proliferation and necrosis. No significant associations were found between IHC scores for immune cells (i.e. lymphocytes and macrophages) and tumour morphology and type. Average factor VIII reactivity was higher in astrocytomas than oligodendrogliomas (P = 0.003).


Subject(s)
Brain Neoplasms/veterinary , Cat Diseases/immunology , Glioma/veterinary , Immunohistochemistry/methods , Tumor Microenvironment/immunology , Animals , Cat Diseases/pathology , Cats , Female , Male , Retrospective Studies
4.
Scand J Med Sci Sports ; 28(4): 1320-1338, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29239047

ABSTRACT

Movement variability during repetitive performance of a dynamic activity (eg, running, jumping, kicking) is considered an integral characteristic of optimal movement execution; however, its relationship with musculo-skeletal injury is not known. The primary aim of this study was to review published comparison trials to determine whether movement variability differs between uninjured controls and subjects with a lower limb musculo-skeletal injury. A systematic search of online databases; MEDLINE, Sports Discus, Scopus, and Web of Science was conducted from July to November 2016. Studies were selected if they (a) included participants with a lower limb injury, (b) compared injured participants to uninjured controls, (c) examined movement variability for at least one dependent variable, and (d) provided a statistical between-group comparison when comparing measures of movement variability. Studies were excluded if they (a) investigated neurological disorders, (b) examined musculo-skeletal injury in the upper extremity or spine, and (c) used nonlinear measures to examine variability (ie, complexity). A significant difference between injured and uninjured populations was reported in 73% of the included studies, and of these, 64% reported greater movement variability in the injured group. This is the first systematic review with a best-evidence synthesis investigating the association between movement variability and musculo-skeletal injury. Findings suggest that movement variability in those with a musculo-skeletal injury differs from uninjured individuals. Interestingly, there was an overall trend toward greater movement variability being associated with the injured groups, although it should be noted that this trend was not consistent across all subcategories (eg, injury type). For a clearer insight into the clinical application of variability, greater methodological homogeneity is required and prospective research is recommended.


Subject(s)
Leg Injuries/physiopathology , Movement , Musculoskeletal System/injuries , Range of Motion, Articular , Biomechanical Phenomena , Case-Control Studies , Humans
5.
Aust Vet J ; 95(8): 294-298, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28749028

ABSTRACT

CASE REPORT: We describe the MRI appearance and surgical outcome of a rare neuroendodermal cyst in the fourth ventricle of a German Shorthaired Pointer. The dog presented with uncoordinated gait and occasional falling that increased when she became excited. The MRI appearance is shown and the surgical treatment described. Recurrence occurred on two occasions and the dog was euthanased. CONCLUSION: Recurrence of these cysts is highly likely unless there is complete surgical resection.


Subject(s)
Cysts/veterinary , Fourth Ventricle , Magnetic Resonance Imaging/veterinary , Neoplasm Recurrence, Local/surgery , Animals , Cysts/surgery , Dogs , Endoderm , Female
6.
J Biomech ; 56: 83-88, 2017 05 03.
Article in English | MEDLINE | ID: mdl-28372796

ABSTRACT

A theoretical and experimental nonlinear analysis of cellular response/displacement to ultrasound excitations is presented. Linear cell models can predict the resonant frequency (fR∼5MHz), but only a nonlinear analysis can reveal the amount of mechanical energy that couples into the cell and the bifurcation behavior of the cell when it is excited near resonance. The cell dynamics is described by the nonlinear viscoelastic constitutive behavior of the cytoplasm, nucleus and their respective membranes, in the presence of a fluid with an oscillating pressure field. The method of multiple scales is used to derive the amplitude of oscillation of the cytoplasm and nucleus as a function of frequency. A major finding is the existence of multiple solutions for a range of sub-resonant frequencies. At positive detuning (f>fR), the mechanical energy that couples into the cell is small, it is higher at resonance but significantly higher at sub-resonant frequencies in the multiplicity range. Experimentally it was shown when 3.5MHz is approached sub- and supra-resonance and 6.5MHz is approached sub-resonance, gene expression was statistically higher than that when stimulated directly. Thus, there exists an optimal range of frequencies for ultrasound treatment - in the region of multiplicity where deformation and thus mechanical energy coupling is maximized. The ultrasound protocol must be designed to operate at the solution associated with the higher mechanical energy - thus the start-up conditions should be in the domain of attraction of the high energy solution.


Subject(s)
Cell Communication/physiology , Chondrocytes/physiology , Acoustics , Animals , Cattle , Cells, Cultured , Nonlinear Dynamics , Pressure , Ultrasonography , Vibration
7.
J Small Anim Pract ; 58(10): 589-592, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28379624

ABSTRACT

An 11-year-old male castrated domestic shorthair cat presented with left central vestibular dysfunction. Magnetic resonance imaging of the brain revealed a large, extra-parenchymal, strongly contrast-enhancing mass at the level of the left cerebellopontine angle and compressing the cerebellum and brainstem. The mass was surgically excised via left rostral and sub-tentorial craniectomies and histopathology revealed an epithelial neoplasm composed of anastomosing cords of neoplastic cells that contained large amounts of finely granular hypereosinophilic cytoplasm and round nuclei. The cytoplasmic granules were variably positive with periodic acid-Schiff and modified Gomori trichrome. Immunohistochemical staining with anti-cytokeratin AE1/AE3 was diffusely positive. Electron microscopy revealed neoplastic cells that were full of electron-dense organelles consistent with mitochondria. This is the first case of a choroid plexus oncocytoma in the central nervous system of any domestic animal species and highlights the role of successful surgical intervention in extra-parenchymal neoplasia in the central nervous system.


Subject(s)
Adenoma, Oxyphilic/veterinary , Cat Diseases/surgery , Choroid Plexus , Magnetic Resonance Imaging/veterinary , Adenoma, Oxyphilic/diagnosis , Adenoma, Oxyphilic/surgery , Animals , Cat Diseases/diagnosis , Cats , Male , Microscopy, Electron , Spinal Cord
8.
J Comp Pathol ; 156(2-3): 162-168, 2017.
Article in English | MEDLINE | ID: mdl-27923479

ABSTRACT

Meningioma is the most common primary brain tumour in the cat. Although most of these tumours are considered to be benign based on histological characteristics, little is known regarding microenvironmental changes associated with the tumour. The characterization of the immune-cell infiltrate in human and canine meningiomas has been described; however, there are no data regarding the cat equivalent. Seventeen formalin-fixed, paraffin wax-embedded samples of feline meningioma were evaluated by light microscopy and immunohistochemistry (IHC) for expression of CD3, Pax5, Iba-1, HLA-DR, MAC387, CD163 and Ki67. Variable immune cell infiltrates were seen in every case. All tumours had moderate numbers of infiltrating CD3+ T lymphocytes. Seven of 17 tumours (41%) had infiltrating PAX5+ B lymphocytes that were often dispersed randomly throughout the neoplasm. Macrophage infiltration was abundant in all tumours with widespread immunoreactivity for Iba-1 and HLA-DR. Most tumours (15/17; 88%) had infiltration by MAC387+ macrophages; however, the number of infiltrating cells per ×400 field varied widely (from 0 to 57). Thirteen of 17 tumours (76%) had infiltration by CD163+ macrophages; however (similar to the MAC387 IHC), several tumours had numerous infiltrating cells. There was a potential weak negative rank correlation between the counts of CD3 and Ki67+ cells (rSp = -0.57; P = 0.018); however, no other rank correlations could be established between types of infiltrating immune cells (all other P ≥0.10). This study establishes evidence for a robust population of immune cells in feline meningioma and indicates that further study is needed to better understand the role of these cells with respect to tumour progression and post-surgical outcome.


Subject(s)
Cat Diseases/immunology , Meningeal Neoplasms/veterinary , Meningioma/veterinary , Animals , Cat Diseases/pathology , Cats , Female , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/immunology , Male
10.
Mol Ecol ; 25(16): 3845-64, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27322873

ABSTRACT

Estimating contemporary genetic structure and population connectivity in marine species is challenging, often compromised by genetic markers that lack adequate sensitivity, and unstructured sampling regimes. We show how these limitations can be overcome via the integration of modern genotyping methods and sampling designs guided by LiDAR and SONAR data sets. Here we explore patterns of gene flow and local genetic structure in a commercially harvested abalone species (Haliotis rubra) from southeastern Australia, where the viability of fishing stocks is believed to be dictated by recruitment from local sources. Using a panel of microsatellite and genomewide SNP markers, we compare allele frequencies across a replicated hierarchical sampling area guided by bathymetric LiDAR imagery. Results indicate high levels of gene flow and no significant genetic structure within or between benthic reef habitats across 1400 km of coastline. These findings differ to those reported for other regions of the fishery indicating that larval supply is likely to be spatially variable, with implications for management and long-term recovery from stock depletion. The study highlights the utility of suitably designed genetic markers and spatially informed sampling strategies for gaining insights into recruitment patterns in benthic marine species, assisting in conservation planning and sustainable management of fisheries.


Subject(s)
Genetics, Population , Mollusca/genetics , Animals , Australia , Fisheries , Gene Flow , Gene Frequency , Genomics , Genotype , Polymorphism, Single Nucleotide
11.
Int J Obes (Lond) ; 40(6): 955-63, 2016 06.
Article in English | MEDLINE | ID: mdl-26975441

ABSTRACT

BACKGROUND/OBJECTIVES: Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible. SUBJECTS/METHODS: C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated. RESULTS: In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity. CONCLUSIONS: This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including 'browning' and enhancement of hepatic mitochondrial function.


Subject(s)
Acetic Acid/chemistry , Adipocytes, Brown/drug effects , Adipogenesis/drug effects , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Fatty Acids/pharmacology , Liver/drug effects , Liver/metabolism , Adipocytes, Brown/metabolism , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Disease Models, Animal , Fatty Acids/chemistry , Lipid Metabolism/drug effects , Male , Mice , Mice, Inbred C57BL , Signal Transduction/drug effects
12.
J Comp Pathol ; 153(2-3): 92-100, 2015.
Article in English | MEDLINE | ID: mdl-26145723

ABSTRACT

Oligodendroglioma is a common glial tumour in the dog. In human neuropathology, the immune cell microenvironment of gliomas has been investigated; however, the nature of the inflammatory cells within canine gliomas is currently unknown. The aim of this study was to determine the nature of the immune cells and determine an association between the inflammatory cells and tumour grade. Thirty-four (18 of grade II and 16 of grade III) formalin-fixed and paraffin wax-embedded samples of canine oligodendroglioma were evaluated by light microscopy and immunohistochemistry for expression of CD3, PAX5, Iba-1, HLA-DR, Mac387 and CD31. Variations in immune cell recruitment and activation were evident in all cases. Infiltrating CD3(+) T lymphocytes were common in most cases. PAX5(+) B lymphocytes were less common and restricted to perivascular cuffs within or around the tumour. Iba-1(+) cells were common within the tumour and formed a dense infiltrate around the tumour in a subset of cases. HLA-DR(+) cells were common within the tumour and in a subset of cases formed perivascular cuffs. Iba-1(+) cells typically had prominent ramified processes suggestive of activated microglia, while the HLA-DR(+) cells had a more rounded morphology typical of amoeboid microglia. Rare Mac387(+) macrophages were found in the tumour parenchyma, while increased numbers of Mac387(+) monocytes were noted within the vasculature. No association or significance was established between the immune cell infiltrate and the grade of the tumour (all P ≥0.16). This study establishes that there is a robust population of immune cells within canine oligodendrogliomas and indicates that further study is needed to determine the role of these cells in tumour pathogenesis and progression.


Subject(s)
Brain Neoplasms/immunology , Dog Diseases/immunology , Inflammation/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Oligodendroglioma/immunology , Animals , Brain Neoplasms/pathology , Dog Diseases/pathology , Dogs , Female , Immunohistochemistry , Inflammation/pathology , Male , Oligodendroglioma/pathology
13.
Respir Physiol Neurobiol ; 210: 38-43, 2015 May.
Article in English | MEDLINE | ID: mdl-25655218

ABSTRACT

BACKGROUND: Sleep disordered breathing may be a risk factor for high altitude illness. Past Antarctic sleep studies suggest that rapid transport from sea level (SL) to the Amundsen Scott South Pole Station (SP, 2835 m) increases risk of Acute Mountain Sickness (AMS). We analyzed sleep studies in 38 healthy polar workers to explore the association between sleep disordered breathing and AMS after rapid transport to the South Pole. METHODS: Subjects completed a baseline questionnaire, performed basic physiology tests, and were evaluated for AMS and medication use using an extended Lake Louise Questionnaire (LLQ) during their first week at the South Pole. Participants were included in this study if they took no medications and underwent polysomnography on their first nights at Sea Level and the South Pole using the Vivometrics LifeShirt(®). Within group changes were assessed with Wilcoxon signed rank tests and between group differences were assessed with Kruskal-Wallis rank sum tests. RESULTS: Overall, 21/38 subjects met criteria for AMS at some time on or prior to the third morning at the South Pole. Subjective poor sleep quality was reported by both AMS (65%) and no AMS (41%) groups. The Apnea Hypopnea Index (AHI) increased significantly in both the AMS and no AMS groups, but the difference in the increase between the two groups was not statistically significant. Increased AHI was not associated with increased AMS symptoms. Previous altitude illness (p=0.06) and residence at low altitudes (p = 0.02) were risk factors for AMS. CONCLUSION: AMS was not significantly associated with sleep architecture changes or increased AHI. However, AHI sharply increased at South Pole (19/38 participants) primarily due to central apneas. Those developing AMS were more likely to have experienced previous problems at altitude and reported living at lowland altitudes within the 3 months prior to rapid transport to the South Pole than those without AMS.


Subject(s)
Altitude Sickness/physiopathology , Sleep Apnea Syndromes/physiopathology , Acute Disease , Adult , Altitude , Antarctic Regions , Cohort Studies , Female , Humans , Male , Monitoring, Ambulatory , Surveys and Questionnaires , Time Factors
14.
Vet Pathol ; 52(4): 732-40, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25367367

ABSTRACT

In rhesus macaques, adenocarcinomas of either the ileocecal junction or colon are common spontaneous tumors in aging populations. The macaque tumors have similar gross and histologic characteristics compared with their human counterpart, but little is known regarding the immunohistochemical expression of proteins that are commonly implicated in the pathogenesis of these tumors in humans. We performed a retrospective review of 22 cases of large intestinal carcinoma in the rhesus macaque and evaluated the expression pattern of a panel of potentially prognostically significant proteins identified from human studies. Histologic characteristics of the tumors included abundant mucin deposition, transmural spread, and lymphatic invasion. All rhesus adenocarcinomas displayed altered expression of 1 or more of CD10, ß-catenin, sirtuin 1, cytokeratin 17, and p53 compared with age-matched controls. Zymographic analysis of active matrix metalloproteinases 2 and 9 in the serum from 5 animals failed to reveal statistically significant differences between adenocarcinoma cases and controls. Based on the data presented herein, large intestinal carcinomas in the macaque share many histomorphologic and immunohistochemical similarities to large intestinal tumors in humans. Further validation of this animal model is considered important for the development of novel therapeutics and a better understanding of the pathogenesis.


Subject(s)
Adenocarcinoma, Mucinous/veterinary , Biomarkers, Tumor/metabolism , Intestinal Neoplasms/veterinary , Monkey Diseases/pathology , Adenocarcinoma, Mucinous/pathology , Animals , Female , Immunohistochemistry/veterinary , Intestinal Mucosa/metabolism , Intestinal Neoplasms/pathology , Intestines/pathology , Macaca mulatta , Male , Mucins/metabolism , Prognosis , Retrospective Studies , beta Catenin/metabolism
15.
Vet Pathol ; 52(1): 217-23, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24686387

ABSTRACT

Peripheral neuropathies are common sequelae to human immunodeficiency virus (HIV) infection in humans and are due to a variety of mechanisms, including direct antiretroviral toxicity, HIV-mediated damage, immune-mediated disorders, and opportunistic viral infections. Rhesus macaques (Macaca mulatta) infected with simian immunodeficiency virus (SIV) remain the most consistent animal model for unraveling the pathogenesis of lentiviral-associated disease and its associated opportunistic infections. Rhesus cytomegalovirus (RhCMV) is the most common opportunistic viral infection in rhesus macaques infected with SIV and causes multiorgan pathology; however, its role in peripheral nerve pathology has not been explored. We have identified 115 coinfected cases with SIV and RhCMV, of which 10 cases of RhCMV-associated facial neuritis were found (8.7% prevalence). Histologic lesions were consistent in all cases and ranged from partial to complete obliteration of the nerves of the tongue, lacrimal gland, and other facial tissues with a mixed inflammatory population of neutrophils and macrophages, of which the latter commonly contained intranuclear inclusion bodies. Luxol fast blue staining and myelin basic protein immunohistochemistry confirmed the progressive myelin loss in the peripheral nerves. Bielschowsky silver stain revealed progressive loss of axons directly related to the severity of inflammation. Double immunohistochemistry with spectral imaging analysis revealed RhCMV-infected macrophages directly associated with the neuritis, and there was no evidence to support RhCMV infection of Schwann cells. These results suggest that peripheral nerve damage is a bystander effect secondary to inflammation rather than a direct infection of Schwann cells and warrants further investigations into the pathogenesis of RhCMV-induced peripheral neuropathy.


Subject(s)
Cytomegalovirus Infections/veterinary , Cytomegalovirus/isolation & purification , Facial Nerve Diseases/veterinary , Opportunistic Infections , Simian Acquired Immunodeficiency Syndrome/complications , Simian Immunodeficiency Virus/isolation & purification , Animals , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/pathology , Cytomegalovirus Infections/virology , Disease Models, Animal , Facial Nerve Diseases/pathology , Facial Nerve Diseases/virology , Immunohistochemistry/veterinary , Macaca mulatta , Peripheral Nervous System/pathology , Simian Acquired Immunodeficiency Syndrome/virology
16.
Gene Ther ; 21(4): 363-70, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24500525

ABSTRACT

Animal and human gene therapy studies utilizing AAV vectors have shown that immune responses to AAV capsid proteins can severely limit transgene expression. The main source of capsid antigen is that associated with the AAV vectors, which can be reduced by stringent vector purification. A second source of AAV capsid proteins is that expressed from cap genes aberrantly packaged into AAV virions during vector production. This antigen source can be eliminated by the use of a cap gene that is too large to be incorporated into an AAV capsid, such as a cap gene containing a large intron (captron gene). Here, we investigated the effects of elimination of cap gene transfer and of vector purification by CsCl gradient centrifugation on AAV vector immunogenicity and expression following intramuscular injection in dogs. We found that both approaches reduced vector immunogenicity and that combining the two produced the lowest immune responses and highest transgene expression. This combined approach enabled the use of a relatively mild immunosuppressive regimen to promote robust micro-dystrophin gene expression in Duchenne muscular dystrophy-affected dogs. Our study shows the importance of minimizing AAV cap gene impurities and indicates that this improvement in AAV vector production may benefit human applications.


Subject(s)
Capsid Proteins/immunology , Immunity, Innate , Muscular Dystrophy, Animal/genetics , Muscular Dystrophy, Duchenne/genetics , Animals , Capsid Proteins/genetics , Dependovirus/genetics , Dependovirus/immunology , Dogs , Gene Expression , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors/immunology , Humans , Models, Animal , Muscular Dystrophy, Animal/immunology , Muscular Dystrophy, Animal/therapy , Muscular Dystrophy, Duchenne/immunology , Muscular Dystrophy, Duchenne/therapy , Virion/immunology
17.
Vet Pathol ; 51(3): 651-8, 2014 May.
Article in English | MEDLINE | ID: mdl-23899691

ABSTRACT

Squirrel monkeys (Saimiri spp) are one of the most consistently used New World primates in biomedical research and are increasingly being used in neuroscience research, including models of drug abuse and addiction. Spontaneous neurologic disease in the squirrel monkey is uncommonly reported but includes various infectious diseases as well as cerebral amyloidosis. Hypernatremia is an extremely serious condition of hyperosmolarity that occurs as a result of water loss, adipsia, or excess sodium intake. Neurologic effects of hypernatremia reflect the cellular dehydration produced by the shift of water from the intracellular fluid space into the hypertonic extracellular fluid space. Severe hypernatremia may result in cerebrocortical laminar necrosis (polioencephalomalacia) in human patients as well as in a number of domestic species, including pigs, poultry, and ruminants. We report the clinical, histopathologic, and immunohistochemical findings of polioencephalomalacia in 13 squirrel monkeys. Polioencephalomalacia in these animals was associated with hypernatremia that was confirmed by serum levels of sodium greater than 180 mmol/L (reference range, 134.0-154.0 mmol/L [mEq/L]). All animals had concurrent diseases or experimental manipulation that predisposed to adipsia. Immunohistochemical investigation using antibodies to neuronal nuclei (NeuN), CNPase, Iba-1, and CD31 revealed necrosis of predominantly cerebral cortical layers 3, 4, and 5 characterized by neuronal degeneration and loss, oligodendrocytic loss, microglial proliferation, and vascular reactivity. The squirrel monkey is exquisitely sensitive to hyperosmolar metabolic disruption and it is associated with laminar cortical necrosis.


Subject(s)
Animals, Laboratory , Encephalomalacia/veterinary , Hypernatremia/veterinary , Monkey Diseases/metabolism , Monkey Diseases/pathology , Saimiri , Animals , Encephalomalacia/etiology , Hypernatremia/blood , Hypernatremia/complications , Immunohistochemistry/veterinary , Necrosis
18.
Neuroscience ; 255: 246-54, 2013.
Article in English | MEDLINE | ID: mdl-24120554

ABSTRACT

Responses during a simple reaction time task are influenced by temporal expectation, or the ability to anticipate when a stimulus occurs in time. Here, we test the hypothesis that prefrontal D1 dopamine signaling is necessary for temporal expectation during simple reaction time task performance. We depleted dopamine projections to the medial prefrontal circuits by infusing 6-hydroxidopamine, a selective neurotoxin, into the ventral tegmental area (VTA) of rats, and studied their performance on a simple reaction time task with two delays. VTA dopamine depletion did not change movements or learning of the reaction time task. However, VTA dopamine-depleted animals did not develop delay-dependent speeding of reaction times, suggesting that mesocortical dopamine signaling is required for temporal expectation. Next, we manipulated dopamine signaling within the medial prefrontal cortex using local pharmacology. We found that SCH23390, a D1-type dopamine receptor antagonist, specifically attenuated delay-dependent speeding, while sulpiride, a D2-type receptor antagonist, did not. These data suggest that prefrontal D1 dopamine signaling is necessary for temporal expectation during performance of a simple reaction time task. Our findings provide insight into temporal processing of the prefrontal cortex, and how dopamine signaling influences prefrontal circuits that guide goal-directed behavior.


Subject(s)
Anticipation, Psychological/physiology , Dopamine/metabolism , Reaction Time/physiology , Receptors, Dopamine D1/metabolism , Signal Transduction/physiology , Ventral Tegmental Area/metabolism , Animals , Rats , Rats, Long-Evans
19.
Neuroscience ; 252: 337-45, 2013 Nov 12.
Article in English | MEDLINE | ID: mdl-23962648

ABSTRACT

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 µg/µl) or N-methyl-d-aspartic acid (NMDA; 2 µg/µl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 µg/µl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 µg/µl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder.


Subject(s)
Dopamine/metabolism , Nucleus Accumbens/physiology , Receptors, Ionotropic Glutamate/physiology , Rhombencephalon/physiology , Synaptic Transmission/physiology , Ventral Tegmental Area/physiology , Animals , Electrophysiological Phenomena , Male , Microelectrodes , Rats , Rats, Wistar
20.
Vet Pathol ; 50(6): 1145-53, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23839235

ABSTRACT

A workshop on Emerging Respiratory Viral Infections and Spontaneous Diseases in nonhuman primates was sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology, held December 1-5, 2012, in Seattle, Washington. The session had platform presentations from Drs Karen Terio, Thijs Kuiken, Guy Boivin, and Robert Palermo that focused on naturally occurring influenza, human respiratory syncytial virus, and metapneumovirus in wild and zoo-housed great apes; the molecular biology and pathology of these viral respiratory diseases in nonhuman primate (NHP) models; and the therapeutic and vaccine approaches to prevention and control of these emerging respiratory viral infections. These formal presentations were followed by presentations of 14 unique case studies of rare or newly observed spontaneous lesions in NHPs (see online files for access to digital whole-slide images corresponding to each case report at http://scanscope.com/ACVP%20Slide%20Seminars/2012/Primate%20Pathology/view.apml). The session was attended by meeting participants that included students, pathology trainees, and experienced pathologists from academia and industry with an interest in respiratory and spontaneous diseases of NHPs.


Subject(s)
Macaca , Pan troglodytes , Papio , Primate Diseases/virology , Respiratory Tract Infections/veterinary , Virus Diseases/veterinary , Animals , Female , Macaca fascicularis , Macaca mulatta , Macaca nemestrina , Male , Respiratory Tract Infections/virology , Virus Diseases/virology
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