Characterization of nestin expression in the spinal cord of GFP transgenic mice after peripheral nerve injury

We have previously reported that hair follicles contain multipotent stem cells which express nestin. The nestin-expressing cells form the hair follicle sensory nerve. In vitro, the nestin-expressing hair follicle cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, the sciatic nerve was excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP mice). The ND-GFP cells of the sciatic nerve were also found to be multipotent as the ND-GFP cells in the hair follicle. When the ND-GFP cells in the mouse sciatic nerve cultured on Gelfoam® and were imaged by confocal microscopy, they were observed forming fibers extending the nerve. The fibers consisted of ND-GFP-expressing spindle cells, which co-expressed the neuron marker β-III tubulin, the immature Schwann-cell marker p75NTR and TrkB which is associated with neurons. The fibers also contain nestin-negative spherical cells expressing GFAP, a Schwann-cell marker. The β-III tubulin-positive fibers had growth cones on their tips expressing F-actin, indicating they are growing axons. When the sciatic nerve from mice ubiquitously expressing red fluorescent protein (RFP) was co-cultured on Gelfoam® with the sciatic nerve from ND-GFP transgenic mice, the interaction of nerves was observed. Proliferating nestin-expressing cells in the injured sciatic nerve were also observed in vivo. Nestin-expressing cells were also observed in posterior nerves but not in the spinal cord itself, when placed in 3-D Gelfoam® culture. The results of the present report suggest a critical function of nestin-expressing cells in peripheral nerve growth and regeneration.

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“…This report demonstrated that peripheral nerves contain abundant nestin-expressing cells in contrast to the spinal cord [14].…”

Section: Discussionmentioning

confidence: 53%

Nestin-Expressing Stem Cells Promote Nerve Growth in Long-Term 3-Dimensional Gelfoam®-Supported Histoculture

et al. 2013

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“…13,23,33,40 In addition, a recent study that examined nestin activation in response to peripheral nerve injury showed that nestin-expressing cells increase in the dorsal horn in response to nerve injury providing evidence that nestin may be involved in repair mechanisms in the peripheral nervous system. 41 In the present study, we observed very little expression of nestin in the MPG of sham-operated rats while there was an ~10-fold increase in nestin gene expression in the MPG in response to CNI with resultant increased protein expression 48 h post crush injury. These data suggest that nestin is activated relatively early and in a transient fashion in the MPG in response to crush injury.…”

Section: Discussioncontrasting

confidence: 44%

Increased expression of nestin in the major pelvic ganglion following cavernous nerve injury

Kutlu¹,

Ross²,

Schaeffer³

et al. 2011

Int J Impot Res

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In an effort to identify neuronal repair mechanisms of the major pelvic ganglion (MPG), we evaluated changes in the expression of nestin, an intermediate filament protein and neural stem cell marker following cavernous nerve crush injury (CNI). We utilized two groups of Sprague Dawley rats: (i) sham and (ii) bilateral CNI. Erectile responses to cavernous nerve stimulation (CNS) were determined at 48 h in a subset of rats. The MPG was isolated and removed at 48 h after CNI, and nestin immunolocalization, protein levels and RNA expression were evaluated. At 48 h, erectile responses to CNS in CNI rats were substantially reduced (P<0.05; ~70% decrease in intracavernous pressure/mean arterial pressure) compared with sham surgery controls. This coincided with a dramatic 10-fold increase (P<0.05) in nestin messenger RNA expression and protein levels in the MPG of rats with CNI. Immunoflourescence microscopy demonstrated that nestin upregulation after CNI occurred within the ganglion cell bodies and nerve fibers of the MPG. In conclusion, CNI induces nestin in the MPG. These data suggest that nestin may be involved in the regenerative process of the cavernous nerve following crush injury.

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“…L5 spinal nerve transection of Tg(nestin/EGFP) mice, increased both the expression of nestin‐fluorescent adult NPCs in the dorsal horn of the spinal cord and their labeling by the proliferation marker BrdU on the third day after operation (Matsumura et al, ). In slices of the lumber spinal cord, the P2X3R agonist α,β‐methylene ATP increased [Ca 2+ ] i in the NPCs in a PPADS‐antagonizable manner.…”

Section: Proliferation Migration Differentiation and Necrosis/apopmentioning

confidence: 99%

Regulation of adult neural progenitor cell functions by purinergic signaling

Tang

Illéš

2016

Glia

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Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230.

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Characterization of nestin expression in the spinal cord of GFP transgenic mice after peripheral nerve injury

Cited by 17 publications

References 37 publications

Nestin-Expressing Stem Cells Promote Nerve Growth in Long-Term 3-Dimensional Gelfoam®-Supported Histoculture

Nestin-Expressing Stem Cells Promote Nerve Growth in Long-Term 3-Dimensional Gelfoam®-Supported Histoculture

Increased expression of nestin in the major pelvic ganglion following cavernous nerve injury

Regulation of adult neural progenitor cell functions by purinergic signaling

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