57. Changes in profiles of brain cytokines associated with enhanced recruitment of bone marrow-derived cells into the brain in senescence-accelerated mice

Abstract

Neurodegenerative diseases may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) is a model of brain aging that undergoes an early onset cerebral neurodegeneration following immune senescence. We hypothesized that the brain-immune interaction is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow bone marrow transplantation using young and aged SAMP10 and B6 mice as recipients with 5-week-old GFP transgenic B6 mice as donors and analyzed chimeras immunohistochemically 4 months later. Donor’s marrow-derived cells of the myeloid lineage entered discrete brain regions through the attachments of choroid plexus. In chimeric mice with aged SAMP10 mice being used as recipients, larger numbers of marrow cells entered more brain regions than the other groups, especially in the diencephalon. We performed multiplex cytokine assays to determine tissue concentration of 10 cytokines in the diencephalon prepared from young and aged SAMP10 and B6 mice. Aged SAMP10 mice exhibited higher tissue concentrations of IL-6, G-CSF, CCL11, CXCL1 and CXCL10 than the other groups of chimera. Immunohistochemistry revealed that these cytokines were expressed in astrocytic processes of the attachments of choroid plexus, periventricular astrocytes, tanycytes, and hypothalamic neurons. Therefore, the enhanced recruitment of bone marrow-derived cells into the brain may be associated with region-specific changes in profiles of tissue cytokine microenvironment, which represents a manifestation of perturbed brain-immune interaction in SAMP10 mice.