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Seo Y, Kim HS, Shin Y, et al. Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice. Biochim Biophys Acta. 2014;1842(11):2193-203doi: 10.1016/j.bbadis.2014.08.005.
Seo, Y., Kim, H. S., Shin, Y., Kang, I., Choi, S. W., Yu, K. R., Seo, K. W., & Kang, K. S. (2014). Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice. Biochimica et biophysica acta, 1842(11), 2193-203. https://doi.org/10.1016/j.bbadis.2014.08.005
Seo, Yoojin, et al. "Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice." Biochimica et biophysica acta vol. 1842,11 (2014): 2193-203. doi: https://doi.org/10.1016/j.bbadis.2014.08.005
Seo Y, Kim HS, Shin Y, Kang I, Choi SW, Yu KR, Seo KW, Kang KS. Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice. Biochim Biophys Acta. 2014 Nov;1842(11):2193-203. doi: 10.1016/j.bbadis.2014.08.005. Epub 2014 Aug 15. PMID: 25132229.
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Biochim Biophys Acta. 2014 Nov;1842(11):2193-203. doi: 10.1016/j.bbadis.2014.08.005. Epub 2014 Aug 15.

Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice.

Biochimica et biophysica acta

Yoojin Seo, Hyung-Sik Kim, Yooyoung Shin, Insung Kang, Soon Won Choi, Kyung-Rok Yu, Kwang-Won Seo, Kyung-Sun Kang

Affiliations

  1. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
  2. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Institute for Stem Cell and Regenerative Medicine at Kangstem Biotech, Biotechnology Incubating Center, Seoul National University, Seoul 151-742, South Korea.
  3. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
  4. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Institute for Stem Cell and Regenerative Medicine at Kangstem Biotech, Biotechnology Incubating Center, Seoul National University, Seoul 151-742, South Korea. Electronic address: [email protected].
  5. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea. Electronic address: [email protected].

PMID: 25132229 DOI: 10.1016/j.bbadis.2014.08.005

Abstract

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 7weeks 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.

Copyright © 2014 Elsevier B.V. All rights reserved.

Keywords: Cyclosporin A; Microglia; Neurodegeneration; Niemann–Pick disease type C1; Olfaction

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