کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1904726 1534654 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann–Pick disease type C1 mice
ترجمه فارسی عنوان
فعال شدن بیش از حد میکروگیلالی اختلال بویایی را از طریق مانع از بقای نورون های نوزاد در لامپ های بویایی بیماری های نوعی نایمانا انتخاب می کند.
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• Olfactory impairment is accompanied by excessive microgliosis in a murine NPC1 model.
• Microglia reduces OB interneurons by regulating the neuronal survival and apoptosis.
• The maintenance of OB interneuron via SVZ neurogenesis is important for olfaction.
• Anti-inflammatory agent can ameliorate the olfactory dysfunction.

Progressive olfactory impairment is one of the earliest markers of neurodegeneration. However, the underlying mechanism for this dysfunction remains unclear. The present study investigated the possible role of microgliosis in olfactory deficits using a mouse model of Niemann–Pick disease type C1 (NPC1), which is an incurable neurodegenerative disorder with disrupted lipid trafficking. At 7 weeks of age, NPC1 mutants showed a distinct olfactory impairment in an olfactory test compared with age-matched wild-type controls (WT). The marked loss of olfactory sensory neurons within the NPC1 affected olfactory bulb (NPC1-OB) suggests that NPC1 dysfunction impairs olfactory structure. Furthermore, the pool of neuroblasts in the OB was diminished in NPC1 mice despite the intact proliferative capacity of neural stem/progenitor cells in the subventricular zone. Instead, pro-inflammatory proliferating microglia accumulated extensively in the NPC1-OB as the disease progressed. To evaluate the impact of abnormal microglial activation on olfaction in NPC1 mice, a microglial inhibition study was performed using the anti-inflammatory agent Cyclosporin A (CsA). Importantly, long-term CsA treatment in NPC1 mice reduced reactive microgliosis, restored the survival of newly generated neurons in the OB and improved overall performance on the olfactory test. Therefore, our study highlights the possible role of microglia in the regulation of neuronal turnover in the OB and provides insight into the possible therapeutic applications of microglial inhibition in the attenuation or reversal of olfactory impairment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1842, Issue 11, November 2014, Pages 2193–2203
نویسندگان
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