Search

Background: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine. Chronic inflammation induced by amyloid β proteins (Aβ) is one prominent neuropathological feature in Alzheimer's disease (AD) brain., Methods: Elisa, Western blot, and immunohistochemical staining analysis were performed to examine the level of MIF protein in CSF and brain tissues. MTT and LDH assays were used to examine the neurotoxicity, and the Morris Water Maze test was performed to examine the cognitive function in the MIF +/- /APP23 transgenic mice., Results: MIF expression was upregulated in the brain of AD patients and AD model mice. Elevated MIF concentration was detected in the cerebrospinal fluid of AD patients but not in that of the patients suffering from mild cognitive impairment and vascular dementia. Reduced MIF expression impaired learning and memory in the AD model mice. MIF expression largely associates with Aβ deposits and microglia. The binding assay revealed a direct association between MIF and Aβ oligomers. Neurons instead of glial cells were responsible for the secretion of MIF upon stimulation by Aβ oligomers. In addition, overexpression of MIF significantly protected neuronal cells from Aβ-induced cytotoxicity., Conclusion: Our study suggests that neuronal secretion of MIF may serve as a defense mechanism to compensate for declined cognitive function in AD, and increased MIF level could be a potential AD biomarker.

Macrophage migration inhibitory factor (MIF) has been rediscovered as a hormone and immunomodulator as well as a proinflammatory cytokine. We investigated the expression of MIF protein and mRNA in the rat brain using optimized immunohistochemistry and in situ hybridization, respectively. By immunohistochemical analysis, we found that MIF protein was present in the epithelial cells of the choroid plexus and ependymal cells as well as astrocyte-like cells in the cerebral white matter and cortex. Tissue sections double-stained for glial fibrillary acidic protein (GFAP) and MIF revealed the presence of MIF protein in astrocytes, whereas this protein was scarcely identified in the neurons by staining using an anti-MIF antibody. We also measured the MIF content in the cerebrospinal fluid, which was 15.5 +/- 2.5 ng/ml (mean +/- SEM), comparable to the serum MIF value. In contrast, expression of MIF mRNA was found not only in astrocytes but also in neurons by the in situ hybridization technique. These results suggest that MIF plays a pivotal role as an immunomodulatory cytokine for inflammatory reactions and immune responses in the whole central nervous system.