Disturbed distribution of proliferative brain cells during lupus-like disease.
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.
Stanojcic
Mile
M
Department of Psychiatry and Behavioural Neurosciences, McMaster University and The Brain-Body Institute, St Joseph's Healthcare Hamilton, Ont, Canada.
Burstyn-Cohen
Tal
T
Nashi
Nadia
N
Lemke
Greg
G
Sakic
Boris
B
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001284:Atrophy; D001835:Body Weight; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D016923:Cell Death; D002465:Cell Movement; D049109:Cell Proliferation; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000473:pathology*; D009929:Organ Size; D013045:Species Specificity