Myelin—Associated Inhibitory Signaling and Strategies to Overcome Inhibition

Chaudhry, Nagarathnamma; Filbin, Marie T.

doi:10.1038/sj.jcbfm.9600407

Cited by 43 publications

(46 citation statements)

References 101 publications

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“…The reason for this is not known. Lamprey CNS lacks myelin (Bullock et al, 1984), so myelin-associated growth inhibitors that potentially could inhibit axonal regeneration (Chaudhry and Filbin, 2006;Grandpre and Strittmatter, 2001;He and Koprivica, 2004;Liu et al, 2006;Quarles, 2007) are presumably absent in lampreys. Identified giant RS neurons differ from one another in their regenerative abilities, which have been determined previously (Davis and McClellan, 1994a,b;Jacobs et al, 1997;Swain, 1989).…”

Section: Retrograde Cell Death Occurs Selectively In "Bad-regeneratinmentioning

confidence: 99%

Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys

Shifman

Zhang

Selzer

2008

J of Comparative Neurology

122

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There is controversy about whether axotomized neurons undergo death or only severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from complete spinal transection, but only about half of the severed spinal-projecting axons regenerate through the site of injury. The fates of the unregenerated neurons remain unknown, and until now death of axotomized spinal-projecting neurons has not been described in the lamprey brain. We now report that in animals allowed to survive for 12 or more weeks after spinal cord transection, several identified reticulospinal (RS) neurons were missing in Nissl-stained or neurofilament-immunostained brain whole mounts. At earlier times, these neurons were swollen and pale in Nissl-stained preparations. Retrograde fluorescent labeling from the site of transection combined with TUNEL histochemistry suggested that neuronal death, including that of the identified RS neurons, began in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not seen in untransected animals. The TUNEL positivity suggests that some cells were dying by apoptosis. Of special interest, among the identified neurons, this delayed cell death was restricted to neurons that at earlier posttransection times have a low probability of regeneration. These data show that SCI induces delayed cell death in lamprey spinal-projecting neurons and suggest that the reason why some neurons are "bad regenerators" is that they are already undergoing apoptotic cell death. Thus protection from apoptosis may be necessary in order to enhance axonal regeneration after SCI.

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Section: Retrograde Cell Death Occurs Selectively In "Bad-regeneratinmentioning

confidence: 99%

Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys

Shifman

Zhang

Selzer

2008

J of Comparative Neurology

122

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“…Failed adult regeneration can be attributed to both intrinsic and extrinsic factors. In the adult CNS, injury results in the release or deposition of inhibitory molecules within myelin [3–6] and the glial scar [7–9]. A relative insufficiency of neurotrophic signaling also contributes [10].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, neurons decrease in their intrinsic growth capacity as a function of maturity, as reflected by a postnatal decline in ability for rapid neurite extension [11]. While simply blocking the expression or presentation of glial-assocaited inhibitory factors can promote axonal regeneration after injury [6,8], the relative ability of immature neurons to overcome inhibitory cues [12–14] suggest that therapeutic targeting of the factors that influence the intrinsic growth state of the neuron may be effective in regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

The role of soluble adenylyl cyclase in neurite outgrowth

Stiles

Kapiloff

Goldberg

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Axon regeneration in the mature central nervous system is limited by extrinsic inhibitory signals and a postnatal decline in neurons' intrinsic growth capacity. Neuronal levels of the second messenger cAMP are important in regulating both intrinsic growth capacity and neurons' responses to extrinsic factors. Approaches which increase intracellular cAMP in neurons enhance neurite outgrowth and facilitate regeneration after injury. Thus, understanding the factors which affect cAMP in neurons is of potential therapeutic importance. Recently, soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl cyclase, was found to play a key role in neuronal survival and axon growth. sAC is activated by bicarbonate and cations and may translate physiologic signals from metabolism and electrical activity into a neuron's decision to survive or regenerate. Here we critically review the literature surrounding sAC and cAMP signaling in neurons to further elucidate the potential role of sAC signaling in neurite outgrowth and regeneration.

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“…Rac1 and RhoA exert antagonistic effects on growth cone dynamics via their effector-kinases, PAK1 and ROCK, stimulating growth cone motility and inducing collapse, respectively. In the damaged nervous system, myelin-derived inhibitors alter the Rac1 and RhoA signaling equilibrium, augmenting RhoA activity at the expense of Rac1 activity [80,81]. RhoA activation activates the sequential ROCK/LIM kinase/cofilin signaling cascade, resulting in the depolymerization of actin filaments and subsequent growth cone collapse [82].…”

Section: Molecular Determinants Involved In the Dampening Of The Plasmentioning

confidence: 99%