Activity-dependent neuron-glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development
Activity-dependent neuron-glial signaling by ATP and leukemia-inhibitory factor promotes hippocampal glial cell development
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DOI：
10.1017/s1740925x09000076
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发表时间：
2008-01-01
影响因子：
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通讯作者：
Fields, R. Douglas
中科院分区：
文献类型：
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作者：
Cohen, Jonathan E.;Fields, R. Douglas
神经元和星形胶质细胞之间的活动依赖性信号传导有助于神经系统的经验依赖性可塑性和发育。然而，负责神经元-胶质细胞相互作用的机制和这些过程的基础可释放因子还没有很好地理解。促炎细胞因子白血病抑制因子（LIF）在海马中由神经胶质细胞在出生后瞬时表达，并在癫痫发作后通过增强的神经活动迅速上调。为了验证自发神经活动通过LIF信号传导调节海马神经胶质细胞发育的假设，我们在混合海马细胞培养物中用钠通道阻断剂河豚毒素（TTX）结合LIF和嘌呤能信号传导阻断剂阻断自发活动。TTX减少海马细胞培养中表达GFAP的星形胶质细胞的数量。此外，通过P2 Y受体阻断嘌呤能信号传导有助于减少星形胶质细胞的数量。在LIF功能阻断抗体的存在下阻断活性或嘌呤能信号传导并没有进一步减少星形胶质细胞的数量。此外，从LIF -/-小鼠制备的海马细胞培养物具有减少的星形胶质细胞数量，并且不存在促进星形胶质细胞分化的活性依赖性神经元-胶质细胞信号传导。结果表明，内源性LIF是海马星形胶质细胞正常发育所必需的，这一过程是由自发神经冲动活动通过释放ATP来调节的。
Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuron-glial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF -/- mice had reduced numbers of astrocytes and activity-dependent neuron-glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.