Glial Cell Line-Derived Neurotrophic Factor Alters Axon Schwann Cell Units and Promotes Myelination in Unmyelinated Nerve Fibers

Höke, Ahmet; Ho, Tony W.; Crawford, Thomas O.; LeBel, Carl; Hilt, Dana; Griffin, John W.

doi:10.1523/jneurosci.23-02-00561.2003

Cited by 144 publications

(124 citation statements)

References 61 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…If correct, then the prediction is that in the presence of sufficient trophic factors, the unmyelinated atrophic ␣-MNs should also increase in size, myelinate, and contribute to increased numbers of myelinated axons in ventral roots and peripheral nerves. To test this, we treated Bax KO mice with GDNF at doses (daily intraperitoneal injection from P1-P14 at 1 g/g or from P11-P21 with 10 g/g) in excess of those used previously to significantly modify postnatal and adult neuromuscular development Hoke et al, 2003;. Surprisingly, we observed only a modest increase in the number of myelinated motor axons in ventral roots or peripheral nerves (Table 6).…”

Section: Can Gdnf Rescue Bax Ko Motoneurons From Atrophy?mentioning

confidence: 91%

“…Surprisingly, we observed only a modest increase in the number of myelinated motor axons in ventral roots or peripheral nerves (Table 6). Although the GDNF injections may have accelerated the rate of myelination (Hoke et al, 2003), total numbers never significantly exceeded adult values and in no case was the absolute change Ͼ13% (L4 ventral root at P21), whereas complete myelination of the atrophic population after GDNF treatment would have led to an almost fivefold increase.…”

Section: Can Gdnf Rescue Bax Ko Motoneurons From Atrophy?mentioning

confidence: 94%

“…GDNF may regulate myelination by stimulating axons to express neuregulin-1, whose expression levels on axons regulates myelination (Hoke et al, 2003;Nave and Salzer, 2006). Although there was a modest increase in the number of myelinated axons in the L4 VR on P21, the increase did not exceed adult values.…”

Section: Ko Micementioning

confidence: 98%

See 2 more Smart Citations

Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle

Buss

Gould²,

Ma³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

The widespread, massive loss of developing neurons in the central and peripheral nervous system of birds and mammals is generally considered to be an evolutionary adaptation. However, until recently, models for testing both the immediate and long-term consequences of preventing this normal cell loss have not been available. We have taken advantage of several methods for preventing neuronal death in vivo to ask whether rescued neurons [e.g., motoneurons (MNs)] differentiate normally and become functionally incorporated into the nervous system. Although many aspects of MN differentiation occurred normally after the prevention of cell death (including the expression of several motoneuron-specific markers, axon projections into the ventral root and peripheral nerves, ultrastructure, dendritic arborization, and afferent axosomatic synapses), other features of the neuromuscular system (MNs and muscle) were abnormal. The cell bodies and axons of MNs were smaller than normal, many MN axons failed to become myelinated or to form functional synaptic contacts with target muscles, and a subpopulation of rescued cells were transformed from ␣-to ␥-like MNs. Additionally, after the rescue of MNs in myogenin glial cell line-derived neurotrophic factor (MyoGDNF) transgenic mice, myofiber differentiation of extrafusal skeletal muscle was transformed and muscle physiology and motor behaviors were abnormal. In contrast, extrafusal myofiber phenotype, muscle physiology, and (except for muscle strength tests) motor behaviors were all normal after the rescue of MNs by genetic deletion of the proapoptotic gene Bax. However, there was an increase in intrafusal muscle fibers (spindles) in Bax knock-out versus both wild-type and MyoGDNF mice. Together, these data indicate that after the prevention of MN death, the neuromuscular system becomes transformed in novel ways to compensate for the presence of the thousands of excess cells.

show abstract

Section: Can Gdnf Rescue Bax Ko Motoneurons From Atrophy?mentioning

confidence: 91%

Section: Can Gdnf Rescue Bax Ko Motoneurons From Atrophy?mentioning

confidence: 94%

See 1 more Smart Citation

Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle

Buss

Gould²,

Ma³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The partial nervous system tissues were obtained from de-identified aborted fetuses with local IRB (Institutional Review Board) approval. The Schwann cells were then purified by a modified Brockes method [13,14]. Briefly, the dissected nerves were incubated in Hanks Plus (HBSS, 10 mM HEPES, 33.3 mM glucose and 5 μg/ml gentamicin) (Invitrogen Corporation) and collagenase solution for 45 min at 37°C…”

Section: Human Schwann Cell Isolationmentioning

confidence: 99%

The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation

et al. 2008

View full text Add to dashboard Cite

Peripheral nerve regeneration can be enhanced by the stimulation of formation of bands of Büngner prior to implantation. Aligned electrospun poly(ε-caprolactone) (PCL) fibers were fabricated to test their potential to provide contact guidance to human Schwann cells. After 7 days of culture, cell cytoskeleton and nuclei were observed to align and elongate along the fiber axes, emulating the structure of bands of Büngner. Microarray analysis revealed a general down-regulation in expression of neurotrophin and neurotrophic receptors in aligned cells as compared to cells seeded on twodimensional PCL film. Real-time-PCR analyses confirmed the up-regulation of early myelination marker, MAG, and the down-regulation of NCAM-1, a marker of immature Schwann cells. Similar gene expression changes were also observed on cells cultured on randomly-oriented PCL electrospun fibers. However, up-regulation of the myelin-specific gene, P0, was observed only on aligned electrospun fibers, suggesting the propensity of aligned fibers in promoting Schwann cell maturation.

show abstract

“…It remains to be seen whether this is caused by a direct effect of BDNF on the Schwann cells or an indirect effect by promoting NRG release from the neurons. Interestingly, GDNF, which leads to effective NRG release from both motor and sensory axons, can cause nonmyelinating Schwann cells to begin myelinating in adults (Hoke et al, 2003).…”

Section: Rapid Axoglial Communication Through Schwann Cell Neurotrophmentioning

confidence: 99%

Rapid Axoglial Signaling Mediated by Neuregulin and Neurotrophic Factors

Esper¹,

Loeb²

2004

J. Neurosci.

View full text Add to dashboard Cite

During peripheral nervous system development, Schwann cells are precisely matched to the axons that they support. This is mediated by axonal neuregulins that are essential for Schwann cell survival and differentiation. Here, we show that sensory and motor axons rapidly release heparin-binding forms of neuregulin in response to Schwann cell-derived neurotrophic factors in a dose-dependent manner. Neuregulin release occurs within minutes, is saturable, and occurs from axons that were isolated using a newly designed chamber slide apparatus. Although NGF and glial cell line-derived neurotrophic factor (GDNF) were the most potent neurotrophic factors to release neuregulin from sensory neurons, GDNF and BDNF were most potent for motor neurons and were the predominant neuregulin-releasing neurotrophic factors produced by cultured Schwann cells. Comparable levels of neuregulin could be released at a similar rate from neurons after protein kinase C activation with the phorbol ester, phorbol 12-myristate 13-acetate, which has also been shown to promote the cleavage and release of neuregulin from its transmembrane precursor. The rapid release of neuregulin from axons in response to Schwann cell-derived neurotrophic factors may be part of a spatially restricted system of communication at the axoglial interface important for proper peripheral nerve development, function, and repair.

show abstract

Glial Cell Line-Derived Neurotrophic Factor Alters Axon Schwann Cell Units and Promotes Myelination in Unmyelinated Nerve Fibers

Cited by 144 publications

References 61 publications

Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle

Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle

The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation

Rapid Axoglial Signaling Mediated by Neuregulin and Neurotrophic Factors

Contact Info

Product

Resources

About