Schwann cell responses to forskolin and cyclic AMP analogues: comparative study of mouse and rat Schwann cells

Yamada, Hitoshi; Komiyama, Atsushi; Suzuki, Kinuko

doi:10.1016/0006-8993(95)00293-y

Cited by 28 publications

(22 citation statements)

References 26 publications

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“…During development, the period of maximal proliferation of SCs coincides with the period of maximal contact between adjacent SCs (Wanner et al, 2006), and the onset of myelination requires SC segregation and the establishment of an intimate association of the membrane of the myelinating SC with that of the ensheathed axon (Webster et al, 1973). In addition, and confirming previous observations (Sobue et al, 1986; Yamada et al, 1995), we have found that the induction of adult SC re-differentiation requires not only much longer exposure to but also higher doses of cAMP-inducing agents than those required for the stimulatory effect of cAMP on cell proliferation, indicating that cAMP controls proliferation and differentiation through a different mechanism of action. This idea is further supported by the observation that cAMP synergistically enhanced growth factor-dependent proliferation (adjuvant effect), whereas it elicited MG expression independently of growth factors (direct effect).…”

Section: Discussionsupporting

confidence: 91%

Non‐antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re‐differentiation

Monje

Rendon

Athauda

et al. 2008

Glia

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The expression of myelination-associated genes (MGs) can be induced by cyclic adenosine monophosphate (cAMP) elevation in isolated Schwann cells (SCs). To further understand the effect of known SC mitogens in the regulation of SC differentiation, we studied the response of SCs isolated from adult nerves to combined cAMP, growth factors, including neuregulin, and serum. In adult SCs, the induction of MGs by cAMP coincided with the loss of genes expressed in non-myelin-forming SCs and with a change in cell morphology from a bipolar to an expanded epithelial-like shape. Prolonged treatment with high doses of cAMP-stimulating agents, as well as low cell density, was required for the induction of SC differentiation. Stimulation with serum, neuregulin alone, or other growth factors including PDGF, IGF and FGF, increased SC proliferation but did not induce the expression of MGs or the associated morphological change. Most importantly, when these factors were administered in combination with cAMP-stimulating agents, SC proliferation was synergistically increased without reducing the differentiating activity of cAMP. Even though the initiation of DNA synthesis and the induction of differentiation were mostly incompatible events in individual cells, SCs were able to differentiate under conditions that also supported active proliferation. Overall, the results indicate that in the absence of neurons, cAMP can trigger SC redifferentiation concurrently with, but independently of, growth factor signaling.

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Section: Discussionsupporting

confidence: 91%

Non‐antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re‐differentiation

Monje

Rendon

Athauda

et al. 2008

Glia

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“…Since then, numerous reports have demonstrated either a proliferation response or a differentiation response to cAMP, for example, by demonstrating an increase in the expression of P0 (Lemke and Chao, 1988;Morgan et al, 1991), the O4 antigen (Mirsky et al, 1990;Morgan et al, 1991), the myelin promoting transcription factor Oct-6/SCIP (Monuki et al, 1989), and other myelin-related genes. The divergent response to cAMP has been suggested to depend on the levels of cAMP, differentiation requiring a higher concentration of cAMP (Yamada et al, 1995), whereas just a slight increase in the nucleotide is associated with proliferation and cyclin D1 induction (Iacovelli et al, 2007). However, even at relatively low doses of forskolin (1-10 M), an increase in P0 (Monuki et al, 1989) and MBP mRNA was detected (Lemke and Chao, 1988).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase A-Induced Phosphorylation of the p65 Subunit of Nuclear Factor-κB Promotes Schwann Cell Differentiation into a Myelinating Phenotype

Yoon

Korade²,

Carter

2008

J. Neurosci.

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Axon-Schwann cell interactions are critical for myelin formation during peripheral nerve development and regeneration. Axonal contact promotes Schwann cell precursors to differentiate into a myelinating phenotype, and cAMP-elevating agents can mimic this; however, the mechanisms underlying this differentiation are poorly understood. We demonstrated previously that the transcription factor nuclear factor-B (NF-B) is required for myelin formation by Schwann cells (Nickols et al., 2003), although how it is activated during this process remained to be determined. Here, we report that culturing Schwann cells with sensory neurons results in the activation of cAMPdependent protein kinase (PKA), and this kinase phosphorylates the p65 subunit of NF-B at S276. The phosphorylation was also induced in cultured Schwann cells by treatment with forskolin, dibutyryl-cAMP, or by overexpression of a catalytic subunit of PKA, and this increased the transcriptional activity of NF-B. In developing perinatal rat sciatic nerve, the kinetics of p65 phosphorylation at S276 paralleled that of PKA and NF-B activation. To elucidate the role of p65 phosphorylation in myelin formation, we overexpressed an S276A mutant of p65 in cultured Schwann cells, which blocked PKA-mediated transcriptional activation of NF-B. When the Schwann cells expressing the mutant were cocultured with sensory neurons, there was a 45% reduction in the number of myelinated fibers relative to controls, demonstrating a requirement for p65 phosphorylation by PKA during myelin formation.

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“…Another possible explanation is that the different behavior of Schwann cells reflects species differences (rat vs. mouse). We consider this possibility unlikely, even though mouse and rat Schwann cells respond differently to cAMP activating agents, thus suggesting species-specific differences in signal transduction events (Yamada et al, 1995). Finally, it is conceivable that compensatory mechanisms in Schwann cells from MAG-deficient mice enable the Schwann cells to form normal myelin in the absence of MAG.…”

Section: Discussionmentioning

confidence: 91%

MAG-deficient schwann cells myelinate dorsal root ganglion neurons in culture

Carenini

Montag

Schachner

et al. 1998

Glia

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Schwann cell responses to forskolin and cyclic AMP analogues: comparative study of mouse and rat Schwann cells

Cited by 28 publications

References 26 publications

Non‐antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re‐differentiation

Non‐antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re‐differentiation

Protein Kinase A-Induced Phosphorylation of the p65 Subunit of Nuclear Factor-κB Promotes Schwann Cell Differentiation into a Myelinating Phenotype

MAG-deficient schwann cells myelinate dorsal root ganglion neurons in culture

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