Mts1 protein expression in the central nervous system after injury

Abstract

We recently showed that Mts1 is expressed in white matter astrocytes in the rat brain and spinal cord from the first postnatal day. Its expression level declined in the adult CNS, but its topographical localization was maintained. Only white matter astrocytes in the cerebellum did not express Mts1. After dorsal root or sciatic nerve injury, we observed a marked upregulation of Mts1 in the area of the dorsal funiculus undergoing Wallerian degeneration. Here we show that upregulation of Mts1 is a consistent feature of astrocytes in white matter undergoing Wallerian degeneration. In addition, Mts1 is upregulated in astrocytes outlining the lesion site of a penetrating injury to the forebrain, or cerebellum. Gray matter astrocytes did not express Mts1, even after direct injury. In injured brain, we consistently noted a close relationship between Mts1-expressing astrocytes and ED1-positive microglia/macrophages, which are known to be highly motile cells. Mts1 was expressed in the periventricular area and the rostral migratory stream, i.e., sites of ongoing neuroplasticity in adulthood, and was upregulated in these areas after injury. These data suggest that Mts1-expressing astrocytes play a significant role in degenerative events in the mature white matter, interact with phagocytic microglia/macrophages and regulate cell migration and differentiation in areas of the adult brain with a high degree of plasticity.

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).…”

“…In the lesioned brain, S100A4 is upregulated in the white matter astrocytes outlining the trauma site (9) and is also detected in the hippocampus after excitotoxic injury (10). S100A4 is also overexpressed by the astrocytes of the spinal cord adjacent to the site of spinal transection (11).…”

Role of intracellular S100A4 for migration of rat astrocytes

“…This protein is strongly implicated in invasive and metastatic properties of several non-neural tumor cells (Barraclough, 1998;Jenkinson et al, 2004), but its role in normal astrocytes is unknown. However, S100A4 is markedly upregulated after injury to dorsal roots (Kozlova and Lukanidin, 1999), brain (Kozlova and Lukanidin, 2002) or spinal cord (K.H. Zhang et al, 2004), suggesting that this protein is involved in the development of a CNS environment, which is nonpermissive for regeneration (Sandvig et al, 2004).…”

The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

“…Interestingly, S100A4 is also expressed in white matter (WM) astrocytes and myelinated tracts of the intact rat central nervous system (CNS) 20 , and traumatic brain injury (TBI) in rodents induces marked upregulation of both the S100A4 gene 21 and protein 22 . However, the function of S100A4 in the nervous system remains unclear.…”