Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo.
Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo.
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DOI：
10.1186/1756-6606-4-27
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发表时间：
2011-06-17
期刊：
影响因子：
3.6
通讯作者：
Okabe S
中科院分区：
文献类型：
--
作者：
Kondo S;Kohsaka S;Okabe S
外周免疫反应的发作可能会在神经网络中产生持久的改变。最近的研究表明，神经胶质细胞参与突触重塑。因此，推测在外周炎症下，突触和神经胶质的变化都可能发生。我们测试了这种可能性，在体内双光子显微镜下的树突棘诱导外周免疫反应的脂多糖（LPS）治疗的小鼠。我们观察到，在LPS处理的小鼠中，棘较不稳定。脊柱变化的累积逐渐进展，并在LPS治疗后一周内保持较低水平，但在四周时变得明显较大。在LPS处理后超过8周，消除的棘的分数达到初始群体的20%，并且这种持续的不稳定导致总棘密度的降低。我们接下来评估了通过LPS施用的神经胶质活化。小胶质细胞的激活证实了持续增加的Iba1免疫反应性。在LPS给药后两天观察到小胶质细胞的形态学变化，并在一周内部分恢复，但持续很长一段时间。这些结果表明，一个单一的短暂的外周免疫反应对脊髓和小胶质细胞的长期持续加重的影响。脊柱营业额和小胶质细胞在体内的状态的平行持续改变表明存在一种病理机制，维持增强的重塑神经网络周后外周免疫反应。这种病理机制也可能是人类患者脓毒性脑病后长期认知功能障碍的基础。
An episode of peripheral immune response may create long-lasting alterations in the neural network. Recent studies indicate a glial involvement in synaptic remodeling. Therefore it is postulated that both synaptic and glial changes could occur under the peripheral inflammation. We tested this possibility by in vivo two-photon microscopy of dendritic spines after induction of a peripheral immune response by lipopolysaccharide (LPS) treatment of mice. We observed that the spines were less stable in LPS-treated mice. The accumulation of spine changes gradually progressed and remained low over a week after LPS treatment but became significantly larger at four weeks. Over eight weeks after LPS treatment, the fraction of eliminated spines amounted to 20% of the initial population and this persistent destabilization resulted in a reduction of the total spine density. We next evaluated glial activation by LPS administration. Activation of microglia was confirmed by a persistent increase of Iba1 immunoreactivity. Morphological changes in microglia were observed two days after LPS administration and were partially recovered within one week but sustained over a long time period. These results indicate long-lasting aggravating effects of a single transient peripheral immune response on both spines and microglia. The parallel persistent alterations of both spine turnover and the state of microglia in vivo suggest the presence of a pathological mechanism that sustains the enhanced remodeling of neural networks weeks after peripheral immune responses. This pathological mechanism may also underlie long-lasting cognitive dysfunctions after septic encephalopathy in human patients.
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影响因子：
14.8
作者：
Holtmaat, Anthony;Bonhoeffer, Tobias;Chow, David K.;Chuckowree, Jyoti;De Paola, Vincenzo;Hofer, Sonja B.;Huebener, Mark;Keck, Tara;Knott, Graham;Lee, Wei-Chung A.;Mostany, Ricardo;Mrsic-Flogel, Tom D.;Nedivi, Elly;Portera-Cailliau, Carlos;Svoboda, Karel;Trachtenberg, Joshua T.;Wilbrecht, Linda
通讯作者：
Wilbrecht, Linda
影响因子：
6.2
作者：
Imai, Y;Kohsaka, S
通讯作者：
Kohsaka, S
DOI：
10.2174/1568006043481284
发表时间：
2004-03-01
期刊：
Current drug targets. Cardiovascular & haematological disorders
影响因子：
--
作者：
Nakajima, Kazuyuki;Kohsaka, Shinichi
通讯作者：
Kohsaka, Shinichi
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
25
作者：
Murai, KK;Nguyen, LN;Pasquale, EB
通讯作者：
Pasquale, EB