Behavioral heterogeneity in an animal model of neuropsychiatric lupus.
BACKGROUND
Various psychiatric manifestations of unknown etiology are common in systemic autoimmune disease lupus erythematosus (SLE). Profound heterogeneity at clinical and neuropathological levels suggests distinct subpopulations of SLE patients and multiple mechanisms in the pathogenesis of aberrant behavior. Using inbred mice prone to SLE-like condition, we presently examine whether subpopulations of diseased mice can be identified on the basis of their behavioral performance.


METHODS
Hierarchical cluster analysis was used to classify 105 MRL-lpr males into clusters. Multivariate analysis of variance (MANOVA) and discriminant function analysis were used to detect overall differences and identify discriminative variables.


RESULTS
Cluster 1 was characterized by blunted responsiveness to palatable stimulation, as well as increased spleen mass and serum levels of interleukin-1. Cluster 2 comprised of animals with reduced ambulation speed and enlarged spleen. Mice from cluster 3 showed profound dilatation of brain ventricles, reduced brain mass, impaired nutrition and performance in task reflective of emotional reactivity.


CONCLUSIONS
Present results suggest that systemic autoimmunity compromises brain function via non-Mendelian mechanisms. Although neuroactive cytokines may impair reward systems, brain atrophy seems to underlie deficits in ingestive behavior and emotional reactivity. This study supports the hypothesis that multiple neuroimmunological pathways are involved in the etiology of aberrant behavior during SLE-like disease.
Sakic
Boris
B
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Ontario, Canada. sakic@mcmaster.ca
Hanna
Steven E
SE
Millward
Jason M
JM
D000704:Analysis of Variance; D000818:Animals; D015551:Autoimmunity; D001522:Behavior, Animal / Q000502:physiology*; D015992:Body Mass Index; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood* / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D013154:Spleen / Q000473:pathology
D016207:Cytokines