Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice.

Previous studies have demonstrated that interleukin-2 knockout (KO) mice exhibit alterations in hippocampal cytoarchitecture. Several lines of evidence suggest that these variations may result from immune dysregulation and/or autoimmunity. Thus, this study sought to compare adult IL-2 KO mice and wild-type littermates (8-12 weeks of age), the age where differences in hippocampal cytoarchitecture have previously been observed, for differences in measures of neuroimmunological status in the hippocampus.

IL-2 deficiency results in altered septal and hippocampal cytoarchitecture: relation to development and neurotrophins.

We have found previously that brain IL-2 receptors are enriched in the hippocampal formation, and that loss of this cytokine results in cytoarchitectural alterations in the hippocampus and septum and related behavioral changes in IL-2 knockout (IL-2 KO) mice. These alterations included decreased cholinergic somata in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) and decreased distance across the infrapyramidal (IP) granule cell layer (GCL) of the dentate gyrus (DG). To extend our previous findings, several experiments were conducted comparing IL-2 KO mice and wild-type littermates to determine (1) whether the GABAergic projection neurons of IL-2 KO mice in this region were also affected; (2) if the reduction in septal cholinergic projection neurons found in adult IL-2 KO mice is present at weaning (and prior to the development of peripheral autoimmune disease); and (3) if loss of IL-2 may result in changes in the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), involved in maintenance of hippocampal neurons.

Alterations in septohippocampal cholinergic neurons resulting from interleukin-2 gene knockout.

Interleukin-2 (IL-2) has potent effects on acetylcholine (ACh) release from septohippocampal cholinergic neurons and trophic effects on fetal septal and hippocampal neuronal cultures. Previous work from our lab showed that the absence of endogenous IL-2 leads to impaired hippocampal neurodevelopment and related behaviors. We sought to extend this work by testing the hypotheses that the loss of IL-2 would result in reductions in cholinergic septohippocampal neuron cell number and the density of cholinergic axons found in the hippocampus of IL-2 knockout mice.

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.