title: Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. kondo@med.kyushu-u.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides