Reduced Proliferation of Oligodendrocyte Progenitor Cells in the Postnatal Brain of Dystonia Musculorum Mice
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ORIGINAL PAPER
Reduced Proliferation of Oligodendrocyte Progenitor Cells in the Postnatal Brain of Dystonia Musculorum Mice M. Ibrahim Hossain1,2 · Masao Horie1,3 · Hirohide Takebayashi1
Received: 6 May 2017 / Revised: 14 June 2017 / Accepted: 23 June 2017 © Springer Science+Business Media, LLC 2017
Abstract Dystonia musculorum (dt) mice show sensory neurodegeneration and movement disorder, such as dystonia and cerebellar ataxia. The causative gene Dystonin (Dst) encodes a cytoskeleton linker protein. Although sensory neurodegeneration has been well studied, glial cell responses in the central nervous system (CNS) are poorly understood. Here, we investigated cell proliferation in the CNS of DstGt homozygous mice using newly generated in situ hybridization (ISH) probes—Ki-67 and proliferating cell nuclear antigen (PCNA) probes—both of which effectively detect proliferating cells. We found that Ki67-positive cells were significantly decreased in the corpus callosum and thalamus of dt brain at postnatal day 21 (P21). There is a similar but not significant tendency at postnatal day 14 (P14) in the dt brain. We also confirmed the reduced proliferation by PCNA ISH and Ki-67 immunohistochemistry. Double staining with cell-type-specific markers revealed that proliferating cells are oligodendrocyte progenitor cells (OPCs) in both wild-type and dt brain. We also observed a reduced number of Olig2-positive cells Electronic supplementary material The online version of this article (doi:10.1007/s11064-017-2342-5) contains supplementary material, which is available to authorized users. * Hirohide Takebayashi [email protected]‑u.ac.jp 1
Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951‑8510, Japan
2
Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
3
Present Address: Department of Morphological Sciences, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890–8544, Japan
in the corpus callosum of DstGt homozygous mice at P21, indicating that reduced proliferation resulted in a reduced number of OPCs. Our data indicate that OPCs proliferation is reduced in the dt mouse brain at the postnatal stage and that it subsequently results in the reduced number of OPCs. Keywords Oligodendrocyte precursor cells (OPCs) · Proliferation · In situ hybridization · Mki67 · Dystonia musculorum mice · Dystonin (Dst)
Introduction Proliferating glial cells, mostly oligodendrocyte progenitor cells (OPCs), are present in the postnatal CNS parenchyma. OPCs are generated at restricted regions of the embryonic neural tube [1–3]. They migrate, proliferate until postnatal stages, and then differentiate into oligodendrocytes (OLs) at 2–3 weeks of age during mouse development [4–6]. OPCs express platelet-derived growth factor receptor α (PDGFRα) [7], NG2 chondroitin sulfate proteoglycan [8–10], and Olig1/Olig2 transcription factors [11–13]. In routine pathology, Ki-67 immunoshistochemis
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