Neurotrophic Factor Receptors and Their Signal Transduction Capabilities in Rat Astrocytes

Abstract

Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFR alpha) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte.

Neurotrophin receptor p75NTR mediates Huntington’s disease–associated synaptic and memory dysfunction

“…Besides p75 NTR expression in neurons, it has been reported that astrocytes induce p75 NTR expression after different types of injury (36,86,87). Increased levels of p75 NTR have been detected in both neurons and astrocytes in the hippocampal CA3 region after seizures (37).…”

The Complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor Receptor α Up-Regulates Connexin43 and Intercellular Coupling in Astrocytes via the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Pathway

“…Because astrocytes can be found in "normal" and "reactive" states both in vitro and in vivo (reviewed by Wu and Schwartz, 1998), the physiological condition of these cells may confound the observed responses to CNTF. Whereas normal astrocytes lack CNTFR␣ expression, reactive astrocytes express both mRNA and protein for CNTFR␣ (Ip et al, 1993;Rudge et al, 1994;Duberley et al, 1995). Therefore, unlike their normal counterparts, reactive astrocytes may be responsive to CNTF.…”

Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons

“…The CNTFRα is exclusively expressed in neurons (20), while the CNTF functional receptors (gp130 and LIFRβ) are mainly detected in astrocytes. This suggests that these factors may serve as an action target of CNTF (21). According to the dose-response and time-course experiments, the maximal stimulation of CNTF on astrocytes was observed at 50 ng/ml and the 48-h time-point (22).…”