Activation of glial cells in the spinal cord of Niemann-Pick disease type C1 mice

YANG En-hui QIAO Liang LIN Jun-tang* YAN Xin*

doi:10.16098/j.issn.0529-1356.2017.03.003

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Acta Anatomica Sinica ›› 2017, Vol. 48 ›› Issue (3) : 260-265. DOI: 10.16098/j.issn.0529-1356.2017.03.003

Neurobiology

Activation of glial cells in the spinal cord of Niemann-Pick disease type C1 mice

YANG En-hui^{1, 2} QIAO Liang^{1, 2} LIN Jun-tang ^{1, 2*} YAN Xin ^{1, 2*}

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Abstract

Objective To explore the impact of Niemann-pick disease type C1 (NPC1) on the developing spinal cord by observing the activation of astrocytes and microglia in different segments of Npc1^-/- spinal cord. Methods Npc1^+/- mice bred to generate Npc1^-/- mice （n=3）and wild type mice (Npc1^+/+ )（n=3）, and the mice genotypes were detected by PCR. Immunofluorescent staining was performed on different levels of spinal cord (cervical, thoracic, lumbar, sacrum) and the activations of astrocytes and microglia were compared between Npc1-/- and Npc1+/+ mice at the postnatal day 35. Double Immunofluorescent staining using GFAP and F4/80 with interleukin-1β(IL-1β) investigated the distribution of IL-1β in the Npc1-/- spinal cord. IL-1β, SMI31 and phos-tau were detected by Western blotting. Results GFAP and F4/80 immunofluorescent staining indicated a significantly increased glial activation (P<0.05) in both dorsal and ventral horn of Npc1^-/- spinal cord, which was associated with enhanced IL-1β expression in the glial cells. Western blotting indicated that an up-regulation of phosphorylated neurofilaments and tau protein resulted in axon accumulation in NPC1^-/- spinal cord. Conclusion Our data show pathological changes of glial cells in the NPC1^-/- spinal cord, which is the possible reason of neuronal defects in the NPC1^-/- mice.

Key words

Niemann-Pick disease type C1 / Spinal cord / Astrocyte / Microglia / Western blotting / Mouse

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YANG En-hui QIAO Liang LIN Jun-tang YAN Xin. Activation of glial cells in the spinal cord of Niemann-Pick disease type C1 mice[J]. Acta Anatomica Sinica. 2017, 48(3): 260-265 https://doi.org/10.16098/j.issn.0529-1356.2017.03.003

References

［1］Vanier MT, Gissen P, Bauer P, et al. Diagnostic tests for Niemann-Pick disease type C (NP-C): a critical review ［J］. Mol Genet Metab, 2016, 118 (4): 244-254.

［2］Akaboshi S, Yano T, Miyawaki S, et al. A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of NiemannPick disease type C ［J］. Hum Genet, 1997, 99 (3): 350353.

［3］Loftus SK, Morris JA, Carstea ED, et al. Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene ［J］. Science, 1997, 277 (5323): 232-235.

［4］Brown DE, Thrall MA, Walkley SU, et al. Feline Niemann-Pick disease type C ［J］. Am J Pathol, 1994, 144 (6): 1412-1415.

［5］Lee YM, Sun YH. Drosophila as a model to study the role of glia in neurodegeneration ［J］. J Neurogenet, 2015, 29 (2-3): 69-79.

［6］Maragakis NJ, Rothstein JD. Mechanisms of disease: astrocytes in neurodegenerative disease ［J］. Nat Clin Pract Neuro, 2006, 2 (12): 679-689.

［7］Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain ［J］. Nat Neurosci, 2007, 10 (11): 1387-1394. (in Chinese)

［8］Zhou JS, Su LZh, Song TB, et al. Changes in glial cells in the brain of mice with Niemann-Pick disease type C［J］. Journal of Xi’an Jiaotong University(Medical Sience), 2003, 24(6): 569-571. (in Chinese)

周劲松, 苏联珍, 宋天保, 等. C型尼曼-匹克病小鼠脑内胶质细胞的变化［J］. 西安交通大学学报(医学版), 2003, 24 (6): 569-571.

［9］Baudry M, Yao Y, Simmons D, et al. Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia ［J］. Exp Neurol, 2003, 184 (2): 887-903.

［10］Sarna JR, Larouche M, Marzban H, et al. Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease ［J］. J Comp Neurol, 2003, 456 (3): 279-291.

［11］Pressey SN, Smith DA, Wong AM, et al. Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice ［J］. Neurobiol Dis, 2012, 45 (3): 1086-1100.

［12］Yan X, Qiao L, Yang EH, et al. Activity of glial cells in the olfactory bulb of Niemann-Pick diseace type C1 mice［J］. Acta Physiologica Sinica, 2016, 68(2):141-147. (in Chiense)

闫欣, 乔梁, 杨恩慧, 等. C1型尼曼-匹克氏症小鼠嗅球胶质细胞的活性变化［J］. 生理学报, 2016, 68 (02): 141-147.

［13］Hovakimyan M, Meyer A, Lukas J, et al. Olfactory deficits in Niemann-Pick type C1 (NPC1) disease ［J］. PLoS One, 2013, 8 (12): e82216.

［14］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 ［J］. Biochim Biophys Acta, 2014, 1842 (11): 2193-2203.

［15］Yan X, Ma L, Hovakimyan M, et al. Defects in the retina of Niemann-pick type C 1 mutant mice ［J］. BMC Neurosci, 2014, 15: 126.

［16］Yan X, Yang F, Lukas J, et al. Hyperactive glial cells contribute to axonal pathologies in the spinal cord of Npc1 mutant mice ［J］. Glia, 2014, 62 (7): 1024-1040.

［17］Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000) ［J］. Neurochem Res, 2000, 25 (9-10): 1439-1451.

［18］Austyn JM, Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage ［J］. Eur J Immunol, 1981, 11 (10): 805-815.

［19］German DC, Liang CL, Song T, et al. Neurodegeneration in the Niemann-Pick C mouse: glial involvement ［J］. Neurosci, 2002, 109 (3): 437-450.

［20］Cologna SM, Cluzeau CV, Yanjanin NM, et al. Human and mouse neuroinflammation markers in Niemann-Pick disease, type C1 ［J］. J Inherit Metab Dis, 2014, 37 (1): 83-92.

［21］Zhang D, Hu X, Qian L, et al. Astrogliosis in CNS pathologies: is there a role for microglia ［J］ ? Mol Neurobiol, 2010, 41 (2-3): 232-241.

［22］Chen SH, Oyarzabal EA, Sung YF, et al. Microglial regulation of immunological and neuroprotective functions of astroglia ［J］. Glia, 2015, 63 (1): 118-131.