Spatio-temporal expression profile of NGF and the two-receptor system, TrkA and p75NTR, in experimental autoimmune encephalomyelitis

Abstract

Background: Nerve growth factor (NGF) and its receptors, tropomyosin receptor kinase A (TrkA) and panneurotrophin receptor p75 (p75NTR), are known to play bidirectional roles between the immune and nervous system. There are only few studies with inconclusive results concerning the expression pattern and role of NGF, TrkA, and p75NTR (NGF system) under the neuroinflammatory conditions in multiple sclerosis (MS) and its mouse model, the experimental autoimmune encephalomyelitis (EAE). The aim of this study is to investigate the temporal expression in different cell types of NGF system in the central nervous system (CNS) during the EAE course. Methods: EAE was induced in C57BL/6 mice 6-8 weeks old. CNS tissue samples were collected on specific time points: day 10 (D10), days 20-22 (acute phase), and day 50 (chronic phase), compared to controls. Real-time PCR, Western Blot, histochemistry, and immunofluorescence were performed throughout the disease course for the detection of the spatio-temporal expression of the NGF system. Results: Our findings suggest that both NGF and its receptors, TrkA and p75NTR, are upregulated during acute and chronic phase of the EAE model in the inflammatory lesions in the spinal cord. NGF and its receptors were colocalized with NeuN + cells, GAP-43 + axons, GFAP + cells, Arginase1 + cells, and Mac3 + cells. Furthermore, TrkA and p75NTR were sparsely detected on CNPase + cells within the inflammatory lesion. Of high importance is our observation that despite EAE being a T-mediated disease, only NGF and p75NTR were shown to be expressed by B lymphocytes (B220 + cells) and no expression on T lymphocytes was noticed. Conclusion: Our results indicate that the components of the NGF system are subjected to differential regulation during the EAE disease course. The expression pattern of NGF, TrkA, and p75NTR is described in detail, suggesting possible functional roles in neuroprotection, neuroregeneration, and remyelination by direct and indirect effects on the components of the immune system.

TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

“…NGF and its receptors, TrkA and p75 NTR , are upregulated in experimentally induced encephalomyelitis in mice [271], a finding that supports other studies suggesting cross-talk between the nervous system and the immune system via NGF [272][273][274][275][276]. Post-ischemic inflammatory responses are known to cause secondary neuronal damage in animal stroke models.…”

Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis

“…Previous studies have demonstrated the upregulation of proBDNF and its receptor p75 NTR in macrophages, monocytes, and microglia in a variety of neurological conditions, including spinal cord injury 21 and Toxoplasma infection 20 . A more recent study showed that the upregulated p75 NTR was mainly expressed in the anti-inflammatory, but not proinflammatory M1 phenotype microglia in the spinal cord during EAE progression 38 . We have recently demonstrated that proBDNF was preferentially expressed in M2-like monocytes in acute aortic dissection patients 23 .…”

Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis

“…Notably, the increased expression of p75NTR was mainly found in neurons and astrocytes, which is in line with previously reported studies [ 47 , 48 ]. In addition to neurons and astrocytes, p75NTR was also detected on various immune cells, including peripheral mononuclear blood cells and B lymphocytes, mediating a series of neuroinflammatory responses [ 35 , 49 ]. Furthermore, Choi et al reported that IL-1β and TNF-α upregulate p75NTR expression in neurons and astrocytes via the p38MAPK and NF-κB pathway, causing glial cell proliferation and neuronal cell death [ 33 ].…”