Relationship between the development of autoimmunity and sensorimotor gating in MRL-lpr mice with reduced IL-2 production.
MRL-lpr mice develop systemic lupus-like autoimmune disease associated with changes in emotional reactivity and spatial learning and memory. Although the major immunological deficit in MRL-lpr mice is uncontrolled lymphoproliferation associated with a Fas gene mutation, these mice have a marked deficit in interleukin-2 (IL-2) production which, when treated, can prevent the development of autoimmune disease. Moreover, both MRL-lpr and IL-2 knockout mice manifest alterations in hippocampal cytoarchitecture and cognitive behavior. We found previously that IL-2 knockout mice have alterations in prepulse inhibition (PPI), a measure of sensorimotor gating. Thus, the present study sought to test the hypothesis that that PPI would be altered in MRL-lpr mice. Compared to MRL(+/+) control mice, MRL-lpr mice exhibited different patterns of PPI during development. Whereas 7 and 12-week MRL-lpr mice with evidence of autoimmune disease (the onset and early stages, respectively) showed increased PPI, 5 week predisease MRL-lpr mice did not. MRL-lpr mice also exhibited increased acoustic startle reactivity that was independent of autoimmune disease. These behavioral changes were not associated with increased brain expression of the proinflammatory cytokines genes, IL-1alpha and IL-6, CD3, or c-myc-associated apoptosis.
Petitto
John M
JM
McKnight Brain Institute, Departments of Psychiatry, Neuroscience, and Pharmacology, University of Florida, 32610, Gainesville, FL, USA. jpetitto@psych.med.edu
Huang
Zhi
Z
Lo
Jeannette
J
Beck
Ray D
RD
Rinker
Craig
C
Hartemink
David A
DA
D000161:Acoustic Stimulation; D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000172:deficiency*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr / Q000502:physiology*; D009043:Motor Activity; D009420:Nervous System / Q000503:physiopathology; D012016:Reference Values; D013216:Reflex, Startle; D012677:Sensation
D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2