Raddatz Barbara B, Lehmbecker Annika, Kalkuhl Arno, Deschl Ulrich, Baumgärtner Wolfgang, Ulrich Reiner
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riß), Germany.
Int J Dev Neurosci. 2015 May;42:24-36. doi: 10.1016/j.ijdevneu.2015.02.005. Epub 2015 Feb 19.
Postnatal murine spinal cord represents a good model system to study mammalian central nervous system myelination in vivo as a basis for further studies in demyelinating diseases. Transcriptional changes were analyzed in SJL/J mice on postnatal day 0, 14, 49 and 231 (P0, P14, P49, P231) employing Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Additionally, marker gene signatures for astrocyte and oligodendrocyte lineage-stages were defined to study their gene expression in more detail. In addition, immunohistochemistry was used to quantify the abundance of commonly used glial cell markers. 6092 differentially regulated genes (DEGs) were identified. The up-regulated DEGs at P14, P49 and P231 compared to P0 exhibited significantly enriched associations to gene ontology terms such as myelination and lipid metabolic transport and down-regulated DEGs to neurogenesis and axonogenesis. Expression values of marker gene signatures for neural stem cells, oligodendrocyte precursor cells, and developing astrocytes were constantly decreasing, whereas myelinating oligodendrocyte and mature astrocyte markers showed a steady increase. Molecular findings were substantiated by immunohistochemical observations. The transcriptional changes observed are an important reference for future analysis of degenerative and inflammatory conditions in the spinal cord.
产后小鼠脊髓是研究哺乳动物中枢神经系统髓鞘形成的良好体内模型系统,可为脱髓鞘疾病的进一步研究提供基础。使用Affymetrix GeneChip Mouse Genome 430 2.0阵列分析了出生后第0、14、49和231天(P0、P14、P49、P231)的SJL/J小鼠的转录变化。此外,定义了星形胶质细胞和少突胶质细胞谱系阶段的标记基因特征,以更详细地研究它们的基因表达。此外,免疫组织化学用于量化常用神经胶质细胞标记物的丰度。共鉴定出6092个差异调节基因(DEG)。与P0相比,P14、P49和P231上调的DEG与髓鞘形成、脂质代谢转运等基因本体术语有显著丰富的关联,而下调的DEG与神经发生和轴突发生有关。神经干细胞、少突胶质细胞前体细胞和发育中的星形胶质细胞的标记基因特征的表达值持续下降,而髓鞘形成的少突胶质细胞和成熟星形胶质细胞标记物则呈稳定上升。免疫组织化学观察证实了分子研究结果。观察到的转录变化为未来脊髓退行性和炎症性疾病的分析提供了重要参考。