Metastasis‐associated S100A4 (Mts1) protein is expressed in subpopulations of sensory and autonomic neurons and in Schwann cells of the adult rat

Abstract

S100A4 (Mts1) is a member of a family of calcium-binding proteins of the EF-hand type, which are widely expressed in the nervous system, where they appear to be involved in the regulation of neuron survival, plasticity, and response to injury or disease. S100A4 has previously been demonstrated in astrocytes of the white matter and rostral migratory stream of the adult rat. After injury, S100A4 is markedly up-regulated in affected central nervous white matter areas as well as in the periventricular area and rostral migratory stream. Here, we show that S100A4 is expressed in a subpopulation of dorsal root, trigeminal, geniculate, and nodose ganglion cells; in a subpopulation of postganglionic sympathetic and parasympathetic neurons; in chromaffin cells of the adrenal medulla; and in satellite and Schwann cells. In dorsal root ganglia, S100A4-positive cells appear to constitute a subpopulation of small ganglion neurons, a few of which coexpressed calcitonin gene-related peptide (CGRP) and Griffonia simplicifolia agglutinin (GSA) isolectin B4 (B4). S100A4 protein appears to be transported from dorsal root ganglia to the spinal cord, where it is deposited in the tract of Lissauer. After peripheral nerve or dorsal root injury, a few S100A4-positive cells coexpress CGRP, GSA, or galanin. Peripheral nerve or dorsal root injury induces a marked up-regulation of S100A4 expression in satellite cells in the ganglion and in Schwann cells at the injury site and in the distal stump. This pattern of distribution partially overlaps that of the previously studied S100B and S100A6 proteins, indicating a possible functional cooperation between these proteins. The presence of S100A4 in sensory neurons, including their processes in the central nervous system, suggests that S100A4 is involved in propagation of sensory impulses in specific fiber types.

Peptide Mimetic of the S100A4 Protein Modulates Peripheral Nerve Regeneration and Attenuates the Progression of Neuropathy in Myelin Protein P0 Null Mice

“…Moreover, similarity exists between the patterns of S100A4 expression in the CNS and PNS, where the protein is detected in astrocytes and Schwann cells, respectively, and is strongly upregulated after injury (9,17,18). Accordingly, here we found that S100A4 was expressed by Schwann cells and selected axons in the sciatic nerves of both wild-type and P 0 -/-mice ( Figure 6).…”

“…This finding also suggests the intriguing possibility that S100A4, too, may have multiple roles in the lesioned nerve. Indeed, because S100A4 is upregulated immediately proximal to the injury and in the distal stump (18), it is in the position to affect both the axon crossing the lesion site and a subsequent axon regrowth.…”

“…Increased S100A4 levels after injury were also found in a subpopulation of neurons, mainly sensory and autonomic (18). Moreover, S100A4 promoted neurite outgrowth from sensory neurons in vitro (19), and the S100B member of the family was shown to stimulate neurite outgrowth in the rat sciatic nerve (20).…”

“…Although S100A4 has been less investigated in the peripheral nervous system (PNS) than in the CNS, several studies indicate that its expression also increases in myelinating Schwann cells and/or unmyelinating Remak bundles at the injury site after dorsal root or peripheral nerve injury (17,18). Increased S100A4 levels after injury were also found in a subpopulation of neurons, mainly sensory and autonomic (18).…”

Satellite glial cells in sensory ganglia: from form to function

“…Under resting conditions SGCs display low levels of GFAP, but the expression of this protein greatly increases after axonal damage (see Section 11 and Table 1). S100 proteins are not ideal markers for SGCs because a subpopulation of sensory ganglia neurons and also Schwann cells are positive for them [78,145,176]. The possible roles of S100 proteins in sensory ganglia remain to be explored.…”