Tyrosine phosphatase SHP-1 immunoreactivity increases in a subset of astrocytes following deafferentation of the chicken auditory brainstem

Abstract

Proliferation of astrocytes is a dramatic response of the central nervous system (CNS) to injury and disease. Such proliferation results in the formation of the neural/glial scar and the reconstitution of the glial limitans. However, not all astrocytes enter the proliferative cycle following injury, and for those that do, the period of cell division is limited. Little attention has focused on the events that regulate the duration and extent of astrocyte proliferation following damage, but clearly control mechanisms are in place as CNS injury does not result in the continuous astrocyte proliferation seen in glial tumorigenesis. Protein tyrosine phosphorylation has been implicated in both astrocyte proliferation and differentiation and plays an important role in the regulation of the cell cycle in a number of different systems. We have found a small subset of astrocytes in the chick auditory brainstem that are immunopositive for the protein tyrosine phosphatase SHP‐1. SHP‐1 appears to negatively regulate cellular division in the hematopoietic system and is involved in the mitogenic response to various growth factors. Following cochlea removal, there is a marked increase within the auditory brainstem nucleus, nucleus magnocellularis (NM), in both in the number of SHP‐1‐positive astrocytes and the length of their immunopositive fibers. Significantly, those animals showing the greatest increases in SHP‐1 immunoreactivity do not exhibit large amounts of astrocyte proliferation. We hypothesize that the expression of SHP‐1 plays a role in negatively regulating the mitotic behavior of astrocytes following deafferentation. J. Comp. Neurol. 421:199–214, 2000. © 2000 Wiley‐Liss, Inc.

SHP‐1 expression in avian mixed neural/glial cultures

“…As demonstrated in Figure 2A, neurons do not express SHP‐1. This confirms our in vivo data, where auditory brainstem neurons were not found to express SHP‐1 (Lurie et al, 2000). In contrast, SHP‐1 immunoreactivity is expressed in a subset of astrocytes, microglia, and oligodendrocytes in vitro (Fig.…”

“…In this system, the onset of astrocyte proliferation is correlated with significant increases in SHP‐1 immunoreactivity, although the SHP‐1+ cells do not appear to enter the cell cycle. We hypothesize that SHP‐1 is upregulated in some astrocytes in order to prevent them from entering the cell cycle and thus limiting the extent of astrocyte proliferation following injury in vivo (Lurie et al, 2000). In culture, presumably all glial cells have the potential to proliferate, and thus it is not unexpected that SHP‐1 is expressed by a subpopulation of all glial types in order to limit the amount of proliferation that actually occurs.…”

“…SHP‐1 appears to negatively regulate cell division in a many different systems, including the hemopoietic system (Uchida et al, 1993; Zhao et al, 1994; Yi et al, 1993; Cambillau et al, 1995; Lopez et al, 1996, 1997; Mason et al, 1997; Berg et al, 1998; Kozlowski et al, 1998). Our studies demonstrating that SHP‐1 immunoreactivity increases in some astrocytes in response to deafferentation suggest that SHP‐1 may play a role in negatively regulating atrocyte proliferation following injury (Lurie et al, 2000) and may be an important component of the CNS response to injury.…”

Astrocyte-Secreted Factors Modulate a Gradient of Primary Dendritic Arbors in Nucleus Laminaris of the Avian Auditory Brainstem

“…Glial cell bodies are restricted to the margins outside the NL neuropil during embryonic development [27], [28], [29], [30], [31], and GFAP-positive astrocytes extend processes within the dendritic neuropil at the age when dendritic arborization patterns are changing [26]. Several studies have provided evidence to support a role for Bergmann glia in establishing the dendritic arbors of Purkinje cells in the development of the cerebellum [32], [33].…”

Astrocyte‐secreted factors modulate the developmental distribution of inhibitory synapses in nucleus laminaris of the avian auditory brainstem

“…Here we investigated the role of glial cells in the maturation of the inhibitory pathway from SON to NL. Glial cells populate the area around NL in the avian auditory brainstem (Lippe et al, 1980; Deitch and Rubel, 1989; Lurie and Rubel, 1994; Lurie et al, 2000; Feng and Morest, 2006) and glial fibrillary acidic protein (GFAP)-positive astrocytes can first be identified at E15, just ventral to NL (Korn and Cramer, 2008). By E17 these astrocytes surround the NL cell layer and their processes can be found throughout the neuropil and cell bodies.…”