Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the retina in 6- and 22-month-old English setters with progressive blindness, ataxia, and muscle weakness demonstrated a marked accumulation of abnormal cytosomes within neurons and retinal pigmented epithelial cells. Ganglion cells contained abundant cytosomes with evenly spaced stacks of membranes; bipolar and amacrine cell cytosomes consisted of dense, amorphous material with closely spaced configurations of light and dark lines; cytosomes within photoreceptor cells contained faintly staining curved profiles. All three cytosomes resembled those previously reported in brain neurons of CCL dogs. In retinal pigmented epithelial cells, there were prominent accumulations of lamellar fragments, either free in the cytoplasm or incorporated into melanin granules. These retinal abnormalities are likely to be related to deficiences of peroxidase and defects of lipid peroxidation. The pathologic and biochemical changes seen in these dogs are similar in many respects to those reported in human patients with Batten disease. As such, these dogs provide a convenient model for the study disease mechanisms and for therapeutic approaches to blindness in Batten disease.
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PMID:Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. III. Morphologic abnormalities in retinal neurons and retinal pigmented epithelial cells. 735 Jan 37

Human ceroid-lipofuscinosis is marked by blindness, dementia, ataxia, and premature death. A canine model for this disease exists in English setters whose clinical, pathological and biochemical changes resemble the human disorder. In both syndromes, autofluorescent lipopigments, i.e.; lipofuscin and ceroid ("granular", "fingerprint" and/or "curvilinear bodies") are found in the nervous system, viscera, retina, and pigment epithelium (RPE). Retinal neurons of affected animals between 6 and 22 months of age, contain a variety of abnormal intracellular pigment inclusions. Pigment epithelial cells also contain distinctive cytosomes. Electroretinograms from affected animals showed a reduction in b-wave amplitude. Leukocyte, retinal, and RPE peroxidases, were decreased in affected animals, and also showed age-related changes. In the normal canine eye, peroxidase was associated with fractions containing plasma membranes and melanolysosomes. Improved fractionation techniques localized normal peroxidase to "heavy" fractions (1.24-1.28 g/ml), and peroxidase was decreased in these fractions in CCL animals. A new particle containing hexosaminidase, galactosidase, and acid lipase was observed in affected animals. When retinal homogenates from CCL dogs were injected into the vitreous of rabbit eyes they completely abolished the ERG recording. No such change was observed with homogenates from unaffected animals. The accumulation of large numbers of dense bodies in the retina and RPE in dogs with CCL, along with a decrease in peroxidase, suggests an impairment of degradative mechanisms. Furthermore, ceroid appears to be cytotoxic to the retina and RPE. The relationship of these cytotoxic properties to the accumulation of ceroid in the eye, is the subject of our future research.
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PMID:Morphological and biochemical abnormalities in a model of retinal degeneration: Canine ceroid-lipofuscinosis (CCL). 2048 51

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia.
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PMID:Suppression of microglial activation and monocyte infiltration ameliorates cerebellar hemorrhage induced-brain injury and ataxia. 3271 6