Increased expression of colony‐stimulating factor‐1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss

Abstract

Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice. Immunohistochemical studies demonstrated that CSF1 was expressed in astrocytes and neurons in normal mouse spinal cord. In acute EAE, CSF1 expression was significantly increased, especially in astrocytes in peripheral white matter and large motoneurons. High density of activated microglia was observed in the gray matter where motoneurons expressed high-level CSF1 in acute EAE. Significant large motoneuron loss was seen in chronic EAE and the remaining motoneurons with high-level CSF1 were enwrapped by microglia. Viral vector mediated over-expression of CSF1 in spinal neurons induced profound proliferation and activation of microglia at the injection site and microglia enwrapped CSF1-transduced neurons and their neurites. Significant loss of large CSF1-transduced neurons was seen at 2 and 3 weeks post-viral injection. Demyelination in the CSF1-transduced areas was also significant. These results implicate that CSF1 upregulation in CNS may play an important role in the proliferation and activation of microglia in EAE, contributing to neuroinflammation and neurodegeneration. © 2018 Wiley Periodicals, Inc.

Alleviation of neuropathic pain by over-expressing a soluble colony-stimulating factor 1 receptor

“…We first examined the expression of CSF1 protein in the lumbar DRG and spinal cord. In normal mice, the levels of CSF1 in the DRG and spinal cord were rather low ( Fig 3A and H), similar to what we have observed in the spinal cords in normal mice previously reported (Gushchina et al, 2018).…”

“…CSF1R is also one of the receptors for interleukin 34 (IL-34) which plays an important role in the development and maintenance of microglia and Langerhans cells in the epidermis (Greter et al, 2012;Wang et al, 2012). IL-34 is highly expressed in the mouse CNS as we have previously reported (Gushchina et al, 2018).…”

Microglia are necessary for toxin-mediated demyelination and activation of microglia is sufficient to induce demyelination

“…Of note, increased CSF1 levels have been reported to correlate strongly with microglial activation and neuronal loss in EAE (Gushchina et al, 2018). These latter findings suggest CSF1 may promote EAE pathology either by driving increased microglia numbers and/or their transition to a demyelinating phenotype.…”

Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury

“…In a separate study in mice with contusion SCI, animals received 0.5 l intraspinal injections in both the caudal and rostral region of the contused spinal cord using a glass micro glass needle via a microinfusion pump, as previously described (27,60).…”