Neuregulins and ErbB receptors in cultured neonatal astrocytes

Francis, Amy; Raabe, Timothy D.; Wen, Duanzhi; DeVries, George H.

doi:10.1002/(sici)1097-4547(19990815)57:4<487::aid-jnr8>3.0.co;2-w

Cited by 15 publications

(4 citation statements)

References 35 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using a DNA microarray for neurotrophins/receptors, NRG1 mRNA was detected in BMECs, along with BDNF, NGF, FGF, and NT-5 ( Figure 1A). Neuregulin-1 protein expression was found with multiple NRG1-immunoreactive bands corresponding to previously reported isoforms (Cote et al, 2005;Francis et al, 1999;Lebrasseur et al, 2003). Brain microvascular endothelial cells, MVE, and rat whole-brain homogenates all express a similar pattern of NRG-1 immunoreactive bands ( Figure 1B).…”

Section: Neuregulin-1 Signaling Is Present In Human Brain Microvasculsupporting

confidence: 74%

Neuregulin-1 Signaling in Brain Endothelial Cells

Lok

Sardi

Guo

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

NRG1 signaling has multiple functions in neurons and glia. The data in this study demonstrate that NRG1 may also possess significant signaling and cytoprotective properties in human brain endothelial cells (BMECs). NRG1 mRNA and protein expression are present in these cells, and NRG1 receptors erbB2 and erbB3 are phosphorylated in response to NRG1. NRG1 triggers clear biological responses in BMECs – elevated phospho-Akt levels, increased ring formation in a Matrigel assay, and decreased cell death after oxidative injury with H2O2. These data suggest that NRG1 signaling is functional and cytoprotective in BMECs.

show abstract

Section: Neuregulin-1 Signaling Is Present In Human Brain Microvasculsupporting

confidence: 74%

Neuregulin-1 Signaling in Brain Endothelial Cells

Lok

Sardi

Guo

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…The Nrg‐1 antibody that we used for western blotting was able to detect the C‐terminus of the Nrg‐1 α‐isoform and Nrg‐1 β‐isoform (Nrg‐1α, Nrg‐1β1, and Nrg‐1β2) allowing us to assess the overall level of Nrg‐1 protein. Western blotting identified multiple Nrg‐1‐immunoreactive bands corresponding to the Nrg‐1 α‐isoform and Nrg‐1 β‐isoform, as previously reported (Francis et al ., ; Lebrasseur et al ., ; Cote et al ., ; Lemmens et al ., ). We analysed the density of all Nrg‐1 isoforms in tissue, ranging from 150 to 50 kDa for each sample, and normalised the value to the corresponding β‐actin band in each blot.…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of the neuregulin‐1–ErbB network modulates endogenous oligodendrocyte differentiation and preservation after spinal cord injury

Gauthier

Kosciuczyk

Tapley

et al. 2013

Eur J of Neuroscience

101

View full text Add to dashboard Cite

Spinal cord injury (SCI) results in degeneration of oligodendrocytes that leads to demyelination and axonal dysfunction. Replacement of oligodendrocytes is impaired after SCI, owing to the improper endogenous differentiation and maturation of myelinating oligodendrocytes. Here, we report that SCI-induced dysregulation of neuregulin-1 (Nrg-1)-ErbB signaling may underlie the poor replacement of oligodendrocytes. Nrg-1 and its receptors, ErbB-2, ErbB-3, and ErbB-4, play essential roles in several aspects of oligodendrocyte development and physiology. In rats with SCI, we demonstrate that the Nrg-1 level is dramatically reduced at 1 day after injury, with no restoration at later time-points. Our characterisation shows that Nrg-1 is mainly expressed by neurons, axons and oligodendrocytes in the adult spinal cord, and the robust and lasting decrease in its level following SCI reflects the permanent loss of these cells. Neural precursor cells (NPCs) residing in the spinal cord ependyma express ErbB receptors, suggesting that they are responsive to Nrg-1 availability. In vitro, exogenous Nrg-1 enhanced the proliferation and differentiation of spinal NPCs into oligodendrocytes while reducing astrocyte differentiation. In rats with SCI, recombinant human Nrg-1β1 treatment resulted in a significant increase in the number of new oligodendrocytes and the preservation of existing ones after injury. Nrg-1β1 administration also enhanced axonal preservation and attenuated astrogliosis, tumor necrosis factor-α release and tissue degeneration after SCI. The positive effects of Nrg-1β1 treatment were reversed by inhibiting its receptors. Collectively, our data provide strong evidence to suggest an impact of Nrg-1-ErbB signaling on endogenous oligodendrocyte replacement and maintenance in the adult injured spinal cord, and its potential as a therapeutic target for SCI.

show abstract

“…NRG-1 transcripts are found by in situ hybridization in the germinal zone of embryonic day (E) 14 rat and E18 mouse embryos, and the type III transcripts are the most abundant (Corfas et al, 1995;Meyer et al, 1997). In addition, various NRG-1 isoforms are synthesized in vitro by rat sensory neurons, oligodendrocytes, and astrocytes (Raabe et al, 1997;Vartanian et al, 1997;Francis et al, 1999).…”

mentioning

confidence: 99%

Neuregulin Signaling Regulates Neural Precursor Growth and the Generation of OligodendrocytesIn Vitro

et al. 2001

View full text Add to dashboard Cite

Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.

show abstract

Neuregulins and ErbB receptors in cultured neonatal astrocytes

Cited by 15 publications

References 35 publications

Neuregulin-1 Signaling in Brain Endothelial Cells

Neuregulin-1 Signaling in Brain Endothelial Cells

Dysregulation of the neuregulin‐1–ErbB network modulates endogenous oligodendrocyte differentiation and preservation after spinal cord injury

Neuregulin Signaling Regulates Neural Precursor Growth and the Generation of OligodendrocytesIn Vitro

Contact Info

Product

Resources

About