Expression of Macrophage Migration Inhibitory Factor in the Mouse Neocortex and Posterior Piriform Cortices During Postnatal Development

Abstract

Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in a vast array of cellular and biological processes. Abnormal expression of MIF has been implicated in many neurological diseases, including Parkinson's disease, epilepsy, Alzheimer's Disease, stroke, and neuropathic pain. However, the expression patterns of mif transcript and MIF protein from the early postnatal period through adulthood in the mouse brain are still poorly understood. We therefore investigated the temporal and spatial expression of MIF in the mouse neocortex during postnatal development in detail and partially in posterior piriform cortices (pPC). As determined by quantitative real-time PCR (qPCR), mif transcript gradually increased during development, with the highest level noted at postnatal day 30 (P30) followed by a sharp decline at P75. In contrast, Western blotting results showed that MIF increased constantly from P7 to P75. The highest level of MIF was at P75, while the lowest level of MIF was at P7. Immunofluorescence histochemistry revealed that MIF-immunoreactive (ir) cells were within the entire depth of the developed neocortex, and MIF was heterogeneously distributed among cortical cells, especially at P7, P14, P30, and P75; MIF was abundant in the pyramidal layer within pPC. Double immunostaining showed that all the mature neurons were MIF-ir and all the intensely stained MIF-ir cells were parvalbumin positive (Pv +) at adult. Moreover, it was demonstrated that MIF protein localized in the perikaryon, processes, presynaptic structures, and the nucleus in neurons. Taken together, the developmentally regulated expression and the subcellular localization of MIF should form a platform for an analysis of MIF neurodevelopmental biology and MIF-related nerve diseases.

Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

“…The distribution of MIF in the CNS has previously been studied and MIF is present in most cells of the CNS [ 12 , 59 – 61 ]. However, the distribution of HTRA1 in the CNS is relatively unknown although, as mentioned previously, it has been found in both neurons as well as glia [ 33 , 36 ].…”

“…MIF is highly expressed throughout the central nervous system (CNS) and identified in most cells in nervous tissue including neurons, ependymal cells, astrocytes, oligodendrocytes, neural stem cells/progenitor cells, activated microglia, and Schwann cells [ 59 , 62 , 64 , 65 ]. Several previous investigations have suggested that MIF may be involved in nervous system development, though the function of MIF in this setting is far from clear, and receptor as well as binding partner distributions are unknown [ 4 , 12 , 66 ]. To delineate this, we searched for new MIF binding partners in the CNS using a human fetal brain cDNA library and found HTRA1, an enzyme that belongs to a family of four members (the serine proteases 1–4).…”

“…It also binds to insulin and promotes its stability [ 10 ]. During development of the central nervous system (CNS), MIF acts as a neurotrophic growth factor and is involved in stem cell proliferation and neurogenesis as well as inner ear development [ 4 – 6 , 11 , 12 ]. Deletion of MIF in the mouse CNS results in increased anxiety and depression-like behaviors, as well as impaired hippocampus-dependent memory, likely connected to its influence on stem cells [ 4 ].…”

Macrophage migration inhibitory factor as a novel cerebrospinal fluid marker for neurosyphilis among HIV-negative patients

“…Surprisingly, the CSF MIF concentration was significantly higher in late NS, whereas the serum MIF concentration showed no significant difference between early and late NS. This result may have occurred because CSF MIF is synthesized by and released from neurons as well as astrocytes [24] and because late NS affects the CNS parenchyma and leads to MIF release from injured neurons.…”

Profile of MIF in Developing Hippocampus: Association With Cell Proliferation and Neurite Outgrowth

“…The procedures of pCAG-EGFP and pCAG-MIF-MYC construction were identical as previously described ( Zhang et al, 2014 ). In brief, the MYC tag was inserted into the vector pCAG-MCS (Biowit Technologies, China) by using In-Fusion ® HD Cloning Kit (Clontech, United States) according to the manufacturer’s protocol, and then the full-length MIF was cloned into pCAG-MCS-MYC by the traditional cloning method.…”