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Mol Brain. 2011 Jun 17;4:27. doi: 10.1186/1756-6606-4-27.

Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo.

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Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.



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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