Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylmercury (MeHg) is well known to induce auditory disorders such as dysarthria. When we performed a global analysis on the brains of mice exposed to MeHg by magnetic resonance imaging, an increase in the T1 signal in the inferior colliculus (IC), which is localized in the auditory pathway, was observed. Therefore, the purpose of this study is to examine the pathophysiology and auditory dysfunction induced by MeHg, focusing on the IC. Measurement of the auditory brainstem response revealed increases in latency and decreases in threshold in the IC of mice exposed to MeHg for 4 weeks compared with vehicle mice. Incoordination in MeHg-exposed mice was noted after 6 weeks of exposure, indicating that IC dysfunction occurs earlier than incoordination. There was no change in the number of neurons or microglial activity, while the expression of glial fibrillary acidic protein, a marker for astrocytic activity, was elevated in the IC of MeHg-exposed mice after 4 weeks of exposure, indicating that astrogliosis occurs in the IC. Suppression of astrogliosis by treatment with fluorocitrate exacerbated the latency and threshold in the IC evaluated by the auditory brainstem response. Therefore, astrocytes in the IC are considered to play a protective role in the auditory pathway. Astrocytes exposed to MeHg increased the expression of brain-derived neurotrophic factor in the IC, suggesting that astrocytic brain-derived neurotrophic factor is a potent protectant in the IC. This study showed that astrogliosis in the IC could be an adaptive response to MeHg toxicity. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes.
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PMID:Neuroprotective activation of astrocytes by methylmercury exposure in the inferior colliculus. 3155 7

Background: Amyotrophic lateral sclerosis (ALS) is one of the most frequently occurring neurodegenerative diseases affecting speech and swallowing. This preliminary study aimed to investigate whether an autologous lineage-negative stem/progenitor cell therapy applied to ALS patients affects the level of selected trophic and proinflammatory factors, and subsequently improves the articulation. Methods: We enrolled 12 patients with sporadic ALS, who underwent autologous bone marrow-derived lineage negative (LIN-) cells administration into cerebrospinal fluid (CSF). We evaluated patients' articulation using the Frenchay Dysarthria Assessment on days 0 and 28 following the LIN- cells administration. Concentrations of various factors (BDNF, NGF, ANGP-2, VEGF, PDGF-AA, PEDF, COMP-FH, CRP, C3, C4) in CSF were quantified by multiplex fluorescent bead-based immunoassays in the samples collected on the day of LIN- cells administration and 28 days later. On top of this, we assessed levels of BDNF and NGF in the patients' plasma on the day of the injection, three, seven days and three months after the treatment. Results: Of the 12 patients who received the LIN- cell therapy 8 showed short-termed improvement in articulatory functions (group I), which was particularly noticeable in better phonation time, lips and soft palate performance, swallowing reflex and voice loudness. Four patients (group II) did not show substantial improvement. CSF concentrations of BDNF, ANGP-2 and PDGF-AA in group I decreased significantly 28 days after LIN- cells administration. The highest concentration levels of BDNF in group II and NGF in both groups in blood plasma were observed on day 3 following the injection. Conclusions: The outcomes of the LIN- cell application in ALS treatment of articulatory organs are promising. The procedure proved to be safe and feasible. A short-lasting trophic effect of autologous LIN- administration could encourage repeated cell's application in order to sustain their beneficial effects, however this approach needs further investigation.
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PMID:Articulation recovery in ALS patients after lineage-negative adjuvant cell therapy - preliminary report. 3278 71