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Altered neuroendocrine status at the onset of CNS lupus-like disease.

Abstract
Neuropsychiatric (NP) manifestations and brain atrophy are common, etiologically unexplained complications of the systemic autoimmune disease lupus erythematosus (SLE). Similar to patients with NP SLE, behavioral deficits and neurodegeneration occur in aged, lupus-prone MRL/lpr mice. In order to gain a better understanding of the time course and nature of CNS involvement, we compare the neuro-immuno-endocrine profiles of two lupus-prone MRL/lpr stocks, which differ in disease onset and severity. Mice from stock 485 (characterized by early lupus-like manifestations) display blunted responsiveness to palatable solutions and impaired nocturnal activity as early as 7 weeks of age. They also have increased IgG in cerebrospinal fluid (CSF) before high serum autoantibody levels and splenomegaly are detected. Moreover, when compared to age-matched 6825 controls, 485 mice exhibit elevated serum corticosterone, enlarged left adrenal gland, and enhanced haematoxylin/eosin staining in the hypothalamic paraventricular nucleus. Swimming speed and novel object exploration become impaired only when more severe peripheral manifestations are documented in 17 week-old 485 mice. The obtained results suggest that performance deficits during the prodromal phase of NP SLE-like disease are associated with autoantibodies in CSF and asymmetric activation of the hypothalamus-pituitary-adrenal axis. Subsequent deterioration in behavioral performance evolves alongside systemic autoimmunity and inflammation. Although a leaky blood-CSF barrier is a possible explanation, one may hypothesize that, similar to neonatal lupus, maternal antibodies to brain antigens cross blood-placental barrier during embryogenesis and induce early endocrine and behavioral deficits in offspring.
AuthorsGenane Loheswaran, Minesh Kapadia, Matthew Gladman, Sheena Pulapaka, Li Xu, Mile Stanojcic, Boris Sakic
JournalBrain, behavior, and immunity (Brain Behav Immun) Vol. 32 Pg. 86-93 (Aug 2013) ISSN: 1090-2139 [Electronic] Netherlands
PMID23466502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Sucrose
  • Corticosterone
Topics
  • Adrenal Glands (pathology)
  • Animals
  • Autoimmune Diseases (immunology, psychology)
  • Behavior, Animal (physiology)
  • Central Nervous System Diseases (physiopathology, psychology)
  • Cerebral Cortex (pathology)
  • Circadian Rhythm (physiology)
  • Corticosterone (blood)
  • Disease Progression
  • Exploratory Behavior (physiology)
  • Functional Laterality (physiology)
  • Lupus Erythematosus, Systemic (physiopathology, psychology)
  • Male
  • Medulla Oblongata (pathology)
  • Mice
  • Mice, Inbred Strains
  • Neurosecretory Systems (physiopathology)
  • Spleen (immunology, pathology)
  • Sucrose
  • Swimming (psychology)
  • Taste (physiology)

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