Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Department of Ear-Nose-Throat Surgery, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Neuroscience. 2019 Sep 1;415:89-96. doi: 10.1016/j.neuroscience.2019.07.021. Epub 2019 Jul 17.
In response to changes in brain micro-environment caused by aging, microglia could polarize into proinflammatory M1 phenotype and anti-inflammatory M2 phenotype. Besides, astroglia could polarize into A1 phenotype, exhibiting neurotoxicity, or A2 phenotype, showing neuroprotection. This study aimed to investigate the change of glial cells and dopaminergic (DA) neuron in midbrain with age. Two-, 6-, 18- and 28- months old rat brains were collected. The DA neurons were detected using anti-TH and anti-DAT antibodies. The expressions of astroglia markers (glial fibrillary acidic protein, GFAP), microglia markers (ionized calcium binding adaptor molecule 1, Iba-1), M1 markers (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), M2 markers (arginase 1 (Arg1) and IL-10), A1 markers (lipocalin-2 (Lcn2) and complement C3 (C3), A2 markers (brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were examined by real time RT-PCR and Western Blotting. DA neuron expressions decreased in 18-, 28- months old rat brains. In addition, microglia and astroglia have different degrees of activation with age. Besides, M1 markers (TNF-α and IL-1β) increased and M2 markers (Arg1 and IL-10) decreased in aged rats. Furthermore, A2 markers (BDNF and GDNF) decreased and A1 markers (Lcn2 and C3) increased in aged rats. Age induced DA neuron loss and influenced midbrain glial cells phenotypic polarization, which might account for the occurrence and pathogenesis of Parkinson's diseases.
针对衰老引起的大脑微环境变化，小胶质细胞可能会极化成为促炎 M1 表型和抗炎 M2 表型。此外，星形胶质细胞可能会极化成为具有神经毒性的 A1 表型，或具有神经保护作用的 A2 表型。本研究旨在探讨大脑中胶质细胞和多巴胺能（DA）神经元随年龄的变化。收集 2、6、18 和 28 月龄大鼠的大脑。使用抗 TH 和抗 DAT 抗体检测 DA 神经元。通过实时 RT-PCR 和 Western Blotting 检测星形胶质细胞标志物（胶质纤维酸性蛋白，GFAP）、小胶质细胞标志物（离子钙结合衔接分子 1，Iba-1）、M1 标志物（肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）、M2 标志物（精氨酸酶 1（Arg1）和白细胞介素-10（IL-10）、A1 标志物（脂联素-2（Lcn2）和补体 C3（C3）、A2 标志物（脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的表达。结果显示，18、28 月龄大鼠的 DA 神经元表达减少。此外，随着年龄的增长，小胶质细胞和星形胶质细胞有不同程度的激活。此外，老化大鼠的 M1 标志物（TNF-α和 IL-1β）增加，M2 标志物（Arg1 和 IL-10）减少。进一步研究发现，老化大鼠的 A2 标志物（BDNF 和 GDNF）减少，A1 标志物（Lcn2 和 C3）增加。年龄导致 DA 神经元丢失并影响中脑胶质细胞表型极化，这可能是帕金森病发生和发病的原因。
