Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
Exp Neurol. 2012 Jan;233(1):587-94. doi: 10.1016/j.expneurol.2011.11.029. Epub 2011 Dec 1.
We have previously demonstrated a role for the chemokines MCP-1, MIP-1α and GRO-α in directing subventricular zone (SVZ)-derived neural precursor cell migration towards the site of cell death in the adult rodent brain. However the influence of chemokines such as MCP-1, MIP-1α and GRO-α on the differentiation of adult neural precursor cells has not previously been investigated. Further, as the majority of neurological disorders and injuries occur during ageing, it is important to investigate the effect of chemokines on adult neural precursor cell cultures obtained from the ageing brain. This study therefore examined the effect of MCP-1, MIP-1α and GRO-α on SVZ-derived neural precursor cell differentiation in vitro, and assessed whether precursor cells from the middle-aged rat brain (13 months old) follow the same migratory and differential profile as neural precursor cells obtained from the young adult rat brain (2 months old). We observed that each of the chemokines examined generated differing effects in regards to neuronal or glial differentiation. Further, both MIP-1α and GRO-α increased total cell number, suggesting an effect on precursor cell proliferation and/or survival. In agreement with cultures obtained from young adult brains, SVZ-derived neural precursor cells cultured from the middle-aged brain exhibited chemotactic migration in response to a concentration gradient. These results indicate that the chemokines MCP-1, MIP-1α and GRO-α can influence both the migration and fate choice of SVZ-derived neural precursor cells, as well as promoting cell viability. While a response to each of these chemokines is maintained in the middle-aged brain, a distinct age-related alteration in differential fate can be identified.
我们之前已经证明趋化因子 MCP-1、MIP-1α 和 GRO-α 在引导侧脑室下区 (SVZ) 来源的神经前体细胞向成年啮齿动物大脑中细胞死亡部位迁移方面发挥作用。然而，趋化因子如 MCP-1、MIP-1α 和 GRO-α 对成年神经前体细胞分化的影响尚未被研究过。此外，由于大多数神经疾病和损伤发生在衰老过程中，因此研究趋化因子对来自衰老大脑的成年神经前体细胞培养物的影响很重要。因此，本研究检查了 MCP-1、MIP-1α 和 GRO-α 对 SVZ 来源的神经前体细胞体外分化的影响，并评估了来自中年大鼠（13 个月大）大脑的前体细胞是否遵循与来自年轻成年大鼠（2 个月大）大脑的神经前体细胞相同的迁移和分化模式。我们观察到，检查的每种趋化因子在神经元或神经胶质分化方面产生了不同的影响。此外，MIP-1α 和 GRO-α 均增加了总细胞数，表明对前体细胞增殖和/或存活有影响。与来自年轻成年大脑的培养物一致，从中年大脑培养的 SVZ 来源的神经前体细胞对浓度梯度表现出趋化性迁移。这些结果表明，趋化因子 MCP-1、MIP-1α 和 GRO-α 可以影响 SVZ 来源的神经前体细胞的迁移和命运选择，并促进细胞活力。虽然在中年大脑中维持了对每种趋化因子的反应，但可以识别出明显的与年龄相关的分化命运改变。
