β-Catenin Signaling Increases in Proliferating NG2+ Progenitors and Astrocytes during Post-Traumatic Gliogenesis in the Adult Brain

White, Bryan D.; Nathe, Ryan J.; Maris, Don O.; Nguyen, Nghi K.; Goodson, Jamie M.; Moon, Randall T.; Horner, Philip J.

doi:10.1002/stem.268

Cited by 71 publications

(81 citation statements)

References 52 publications

(85 reference statements)

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“…20 Specific changes to the mechanics of the device include an update to the injury probe linkage to include a Lucite platform that is threaded directly in line with the injury probe. This provides a more rigid reference point for the noncontacting position sensor (KD-2306; Kaman Precision Products, Colorado Springs, CO), and allows for rapid modification of the reference gap when injury displacement calibration is modified between mice and rats.…”

Section: Updated Electromagnetic Spinal Cord Injury Devicementioning

confidence: 99%

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

Mondello

Sunshine

Fischedick

et al. 2015

Journal of Neurotrauma

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Cervical spinal cord contusion is the most common human spinal cord injury, yet few rodent models replicate the pathophysiological and functional sequela of this injury. Here, we modified an electromechanical injury device and characterized the behavioral and histological changes occurring in response to a lateralized C4 contusion injury in rats. A key feature of the model includes a non-injurious touch phase where the spinal cord surface is dimpled with a consistent starting force. Animals were either left intact as a control, received a non-injury-producing touch on the surface of the cord (''sham''), or received a 0.6 mm or a 0.8 mm displacement injury. Rats were then tested on the forelimb asymmetry use test, CatWalk, and the Irvine, Beatties, and Bresnahan (IBB) cereal manipulation task to assess proximal and distal upper limb function for 12 weeks. Injuries of moderate (0.6 mm) and large (0.8 mm) displacement showed consistent differences in forelimb asymmetry, metrics of the CatWalk, and sub-scores of the IBB. Overall findings indicated long lasting proximal and distal upper limb deficits following 0.8 mm injury but transient proximal with prolonged distal limb deficits following 0.6 mm injury. Significant differences in loss of ipsilateral unmyelinated and myelinated white matter was detected between injury severities. Demyelination was primarily localized to the dorsolateral region of the hemicord and extended further rostral following 0.8 mm injury. These findings establish the C4 hemi-contusion injury as a consistent, graded model for testing novel treatments targeting forelimb functional recovery.

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Section: Updated Electromagnetic Spinal Cord Injury Devicementioning

confidence: 99%

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

Mondello

Sunshine

Fischedick

et al. 2015

Journal of Neurotrauma

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“…The NG2 cells are widely and abundantly present in the adult brain (Dawson et al, 2000) and can give rise to oligodendrocytes and neurons, but not to astrocytes under the same physiological conditions (Dawson et al, 2003;Dayer et al, 2005;Tamura et al, 2007a). On the other hand, the NG2 cells were reported to generate astrocytes during perinatal development (Zhu et al, 2008;Guo et al, 2009) and in the adult brain and spinal cord which underwent acute injury with neuronal death or gliosis (Hampton et al, 2004;Magnus et al, 2007;Zhao et al, 2009;White et al, 2010). Based on these findings, we investigate here whether astrogenesis occurs in the cerebral cortex following cortical SD, which is a potent stimulus for NG2 cell proliferation without cell death.…”

Section: Introductionmentioning

confidence: 99%

Cortical Spreading Depression Shifts Cell Fate Determination of Progenitor Cells in the Adult Cortex

Tamura

Eguchi

Jin

et al. 2012

J Cereb Blood Flow Metab

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Cortical spreading depression (SD) is propagating neuronal and glial depolarization and is thought to underly the pathophysiology of migraine. We have reported that cortical SD facilitates the proliferative activity of NG2-containing progenitor cells (NG2 cells) that give rise to oligodendrocytes and immature neurons under the physiological conditions in the adult mammalian cortex. Astrocytes have an important role in the maintenance of neuronal functions and alleviate neuronal damage after intense neuronal excitation, including SD and seizures. We here investigated whether SD promotes astrocyte generation from NG2 cells following SD stimuli. Spreading depression was induced by epidural application of 1 mol/L KCl solution in adult rats. We investigated the cell fate of NG2 cells following SD-induced proliferation using 5 0 -bromodeoxyuridine labeling and immunohistochemical analysis. Newly generated astrocytes were observed only in the SD-stimulated cortex, but not in the contralateral cortex or in normal cortex. The astrocytes were generated from proliferating NG2 cells. Astrogenesis depended on the number of SD stimuli, and was accompanied by suppression of oligodendrogenesis. These observations indicate that the cell fate of NG2 cells was shifted from oligodendrocytes to astrocytes depending on SD stimuli, suggesting activitydependent tissue remodeling for maintenance of brain functions.

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“…28 In agreement, SCI has been reported to not promote Wnt canonical activation in BATgal transgenic mice. 32 However, new recent experimental evidences are providing contradictory data in support of Wnt expression, with key roles in both the healthy and damaged spinal cord of adult mice. In this line of research, a recent wide screening in the spinal cord of adult mice has shown a constitutive expression of most Wnt family members, as well as the expression of several Wnt ligands (Wnt1, Wnt3a, Wnt4, and Wnt5a), receptors (Fz1 and Fz2), b-catenin, and, remarkably, Wnt inhibitory factor 1 (Wif1) by neurons and astrocytes as a result of amyotrophic lateral sclerosis progression.…”

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confidence: 99%

Wnts Are Expressed in the Spinal Cord of Adult Mice and Are Differentially Induced after Injury

González-Fernández

Fernández-Martos

Shields

et al. 2014

Journal of Neurotrauma

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The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of most Wnt ligands, inhibitors, receptors, and coreceptors are constitutively expressed in healthy adult mice. After dorsal hemisection, we found significant time-dependent variations, with a prominent upregulation of Wnt inhibitory factor 1 (Wif1). IHC against Frizzled (Fz) 1 and Fz4, as representatives of late and acute upregulated receptors, showed a differential expression in the uninjured spinal cord of Fz1 by neurons and oligodendrocytes and Fz4 by astrocytes. After injury, both receptors were maintained in the same type of cells. Finally, by using BATgal reporter mice, our results revealed active b-catenin signaling in neurons of the dorsal horn and cells of the central canal of uninjured spinal cords, besides a lack of additional SCI-induced activation.In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.

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β-Catenin Signaling Increases in Proliferating NG2+ Progenitors and Astrocytes during Post-Traumatic Gliogenesis in the Adult Brain

Cited by 71 publications

References 52 publications

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

Cortical Spreading Depression Shifts Cell Fate Determination of Progenitor Cells in the Adult Cortex

Wnts Are Expressed in the Spinal Cord of Adult Mice and Are Differentially Induced after Injury

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