Disturbed distribution of proliferative brain cells during lupus-like disease

Mile Stanojcic, Tal Burstyn-Cohen, Nadia Nashi, Greg Lemke, Boris Sakic*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Brain atrophy and neuronal degeneration of unknown etiology are frequent and severe concomitants of the systemic autoimmune disease lupus erythematosus (SLE). Using the murine MRL/lpr model, we examined populations of proliferative brain cells during the development of SLE-like disease and brain atrophy. The disease onset was associated with reduced expression of Ki67 and BrdU proliferation markers in the dorsal part of the rostral migratory stream, enhanced Fluoro Jade C staining in the subgranular zone of the dentate gyrus, and paradoxical increase in density of Ki67+/BrdU- cells in the paraventricular nucleus. Protuberances containing clusters of BrdU+ cells were frequent along the lateral ventricles and in some cases were bridging ventricular walls. Cells infiltrating the choroid plexus were Ki67+/BrdU+, suggesting proliferative leukocytosis in this cerebrospinal fluid-producing organ. The above results further support the hypothesis that systemic autoimmune disease induces complex CNS pathology, including impaired neurogenesis in the hippocampus. Moreover, changes in the paraventricular nucleus implicate a metabolic dysfunction in the hypothalamus-pituitary-adrenal axis, which may account for altered hormonal status and psychiatric manifestations in SLE.

Original languageAmerican English
Pages (from-to)1003-1013
Number of pages11
JournalBrain, Behavior, and Immunity
Issue number7
StatePublished - Oct 2009
Externally publishedYes

Bibliographical note

Funding Information:
We are thankful to Drs. Nicolas Toni, Fred H. Gage, and Jane Foster for constructive comments and John Jepsen for technical assistance. This work was supported by funds from the Canadian Institutes of Health Research.


  • Autoimmunity
  • Brain atrophy
  • Brain cell proliferation
  • Hippocampus
  • Lupus
  • MRL model
  • Neurogenesis


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