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)

Sensorineural hearing loss, ataxia, pyramidal signs, and vestibular deficits characterize superficial siderosis of the central nervous system. This study investigated changes in vestibular function, free radical formation, and phosphorylated cJun expression in the vestibular end organs after middle ear treatment with a ferric chloride (FeCl3) solution. A single injection of 70% FeCl3 solution into the unilateral middle ear cavity caused static vestibular symptoms, such as spontaneous nystagmus and head tilt. Asymmetric expression of c-Fos protein was observed in the bilateral vestibular nuclei and prepositus hypoglossal nuclei within 6 h after injection. Histopathologic examinations revealed partial hair cell loss, degeneration of the supporting stroma, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in the neuroepithelial layer of the crista ampullaris in FeCl3-treated animals. 5-(And-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester and diaminofluorescein-2 diacetate fluorescence and immunoreactivity for nitrotyrosine increased markedly in the sensory neuroepithelial layer and nerve bundles of the crista ampullaris after 2 h. Strong immunoreactivity for phospho-cJun and cJun was observed in the type I hair cells of the crista ampullaris 120 h after injection. Thus, a single short-term treatment with a high concentration of FeCl3 in the unilateral middle ear cavity can induce activation of intracellular signals for cJun protein and oxidative stress through the formation of reactive oxygen species and nitric oxide in vestibular sensory receptors, resulting in vestibular dysfunction. These results suggest that activation of intracellular signals for cJun protein and oxidative stress may be a key component of the pathogenesis of vestibular deficits in patients with superficial siderosis.
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PMID:Vestibular end organ injury induced by middle ear treatment with ferric chloride in rats. 2702 67

Excessive activation of NMDA receptor (NMDAR) signaling within the spinal dorsal horn contributes to central sensitization and the induction and maintenance of pathological pain states. However, direct antagonism of NMDARs produces undesirable side effects which limit their clinical use. NMDAR activation produces central sensitization, in part, by initiating a signaling cascade that activates the enzyme neuronal nitric oxide synthase (nNOS) and generates the signaling molecule nitric oxide. NMDAR-mediated activation of nNOS requires a scaffolding protein, postsynaptic density protein 95kDa (PSD95), which tethers nNOS to NMDARs. Thus, disrupting the protein-protein interaction between PSD95 and nNOS may inhibit pro-nociceptive signaling mechanisms downstream of NMDARs and suppress central sensitization while sparing unwanted side effects associated with NMDAR antagonists. We examined the impact of small molecule PSD95-nNOS protein-protein interaction inhibitors (ZL006, IC87201) on both nociceptive behavior and formalin-evoked Fos protein expression within the lumbar spinal cord of rats. Comparisons were made with ZL007, an inactive analog of ZL006, and the NMDAR antagonist MK-801. IC87201 and ZL006, but not ZL007, suppressed phase 2 of formalin-evoked pain behavior and decreased the number of formalin-induced Fos-like immunoreactive cells in spinal dorsal horn regions associated with nociceptive processing. MK-801 suppressed Fos protein expression in both dorsal and ventral horns. MK-801 produced motor ataxia in the rotarod test whereas IC87201 and ZL006 failed to do so. ZL006 but not ZL007 suppressed paclitaxel-induced mechanical and cold allodynia in a model of chemotherapy-induced neuropathic pain. Co-immunoprecipitation experiments revealed the presence of the PSD95-nNOS complex in lumbar spinal cord of paclitaxel-treated rats, although ZL006 did not reliably disrupt the complex in all subjects. The present findings validate use of putative small molecule PSD95-nNOS protein-protein interaction inhibitors as novel analgesics and demonstrate, for the first time, that these inhibitors suppress inflammation-evoked neuronal activation at the level of the spinal dorsal horn.
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PMID:Small molecule inhibitors of PSD95-nNOS protein-protein interactions suppress formalin-evoked Fos protein expression and nociceptive behavior in rats. 2828 42

Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, immobility episodes, epilepsy and paralysis of the hindlimbs. Taiep had an initial hypomyelination followed by a progressive demyelination associated with an increased expression of some interleukins and their receptors. The pathology correlated with an increase in nitric oxide activity and lipoperoxidation. In base of the above evidences taiep rat is an appropriate model to study neuroimmune interactions. The aim of this study was to analyze the immune responses in male taiep rats after acute infection with Trichinella spiralis. Our results show that there is an important decrease in the number of intestinal larvae in the taiep rat with respect to Sprague-Dawley control rats. We also found differences in the percentage of innate and adaptive immune cell profile in the mesenteric lymphatic nodes and the spleen that correlated with the demyelination process that took place on taiep subjects. Finally, a clear pro-inflammatory cytokine pattern was seen on infected taiep rats, that could be responsible of the decrement in the number of larvae number. These results sustain the theory that neuroimmune interaction is a fundamental process capable of modulating the immune response, particularly against the parasite Trichinella spiralis in an animal model of progressive demyelination due to tubulinopathy, that could be an important mechanism for the clinical course of autoimmune diseases associated with parasite infection.
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PMID:The deficiency of myelin in the mutant taiep rat induces a differential immune response related to protection from the human parasite Trichinella spiralis. 3281 60


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