Regulation of intrinsic neuronal properties for axon growth and regeneration

Rossi, Ferdinando; Gianola, Sara; Corvetti, Luigi

doi:10.1016/j.pneurobio.2006.12.001

Cited by 134 publications

(111 citation statements)

References 360 publications

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“…The development of adequate microneurosurgery techniques for nerve repair has allowed axons to growth out of proximal stump, to cross the wound and to reenter distal stump, thus establishing functional contacts with appropriate targets 1,2 . Cellular events that take place in the nerve region of regenerating fi bers, as well as close to cell bodies (central nervous system in the case of motor neurons, and sensory ganglia in the case of sensory neurons) create the conditions to maintain neuronal trophism which is necessary to fi ber outgrowth.…”

Section: Introductionmentioning

confidence: 99%

“…Cellular events that take place in the nerve region of regenerating fi bers, as well as close to cell bodies (central nervous system in the case of motor neurons, and sensory ganglia in the case of sensory neurons) create the conditions to maintain neuronal trophism which is necessary to fi ber outgrowth. These events however could be involved in the failure of regeneration and in the death of committed neurons 3,2 . Glial cells are the pivotal elements involved in infl ammation, wound, repair and neuroregeneration both in the central and peripheral nervous systems.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, abundant activated astrocytes are encountered in the anterior and posterior horns of the spinal cord after axotomy of sciatic nerve, which contains both sensory and motor fi bers respectively 5 . Reports have been mentioned that the adult sensory and motor neurons are partially resistant to axotomy because postnatal neurons diminish their trophic dependency from the targets thus becoming more dependent from the trophic support supplied by the cell body (autocrine regulation) and also by the neighbor non neuronal cells, particularly the adjacent glial cells, in a paracrine trophic fashion 2,5,9 . Astrocytes are a class of glial cells which react to neuronal injury, becoming activated.…”

Section: Introductionmentioning

confidence: 99%

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Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Dallo¹,

Reichert²,

Júnior³

et al. 2007

Acta Cir. Bras.

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Differential astroglial responses in the spinal cord of rats -ORIGINAL ARTICLE NeuroregenerationDifferential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract. Implications on cell therapy for nerve repair 1 Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada. Implicações na terapia celular para o reparo do nervo ABSTRACT Purpose: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fi ber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. Methods: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantifi ed by means of quantitative image analysis. Results: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may infl uence the functional outcome. The event should be considered during the neurosurgery strategies. Key words: Sciatic nerve lesion. Astrocyte. Neuronal protection. Neuroplasticity. Neuroregeneration. Pain. Review. RESUMOObjetivo: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fi bras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. Métodos: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina t...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Dallo¹,

Reichert²,

Júnior³

et al. 2007

Acta Cir. Bras.

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“…Currently, regenerating damaged axons or facilitating outgrowth of damaged axons is the main approach to promote recovery of connectivity in many neural disorders. 42,43 Our study here, along with the previous reports, provides a possible novel strategy to generate new axons on polarity-established neurons, which might help generate new axons to promote functional recovery in patients with neural injuries. 33,44 Both loss of the MT2 receptor and a decrease in melatonin are highly correlated with Alzheimer's disease, 12,14,15 and the cellular protection of melatonin or MT2 receptor activation has been well clarified.…”

Section: Discussionmentioning

confidence: 62%

The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling

Man

et al. 2014

Cell Death Differ

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The MT2 receptor is a principal type of G protein-coupled receptor that mainly mediates the effects of melatonin. Deficits of melatonin/MT2 signaling have been found in many neurological disorders, including Alzheimer's disease, the most common cause of dementia in the elderly, suggesting that preservation of the MT2 receptor may be beneficial to these neurological disorders. However, direct evidence linking the MT2 receptor to cognition-related synaptic plasticity remains to be established. Here, we report that the MT2 receptor, but not the MT1 receptor, is essential for axonogenesis both in vitro and in vivo. We find that axon formation is retarded in MT2 receptor knockout mice, MT2-shRNA electroporated brain slices or primary neurons treated with an MT2 receptor selective antagonist. Activation of the MT2 receptor promotes axonogenesis that is associated with an enhancement in excitatory synaptic transmission in central neurons. The signaling components downstream of the MT2 receptor consist of the Akt/GSK-3β/CRMP-2 cascade. The MT2 receptor C-terminal motif binds to Akt directly. Either inhibition of the MT2 receptor or disruption of MT2 receptor-Akt binding reduces axonogenesis and synaptic transmission. Our data suggest that the MT2 receptor activates Akt/GSK-3β/CRMP-2 signaling and is necessary and sufficient to mediate functional axonogenesis and synaptic formation in central neurons. Synaptic circuits are established at the sites of axon-dendritic, axon-somatic or axon-axonal contact, in which functional axonogenesis is a critical step. 1 Axonogenesis can be regulated by many intracellular signals that involve cytoskeletal rearrangements, 2 local protein degradation, 3 as well as diffusional barriers. 4 Additionally, several extracellular neurotrophic factors and hormones have also been shown to have a role in axon guidance and synaptic formation in central neurons. 5,6 To date, the role of melatonin and its receptors in axonogenesis remains unclear. Most of the biological functions of melatonin are mediated by its two receptors, MT1 and MT2 receptors, both of them belong to the G protein-coupled receptor (GPCR) subfamily and are widely expressed throughout the central nervous system (CNS). 7 Activation of the MT2 receptor in response to melatonin is critical for controlling circadian rhythms 7 and regulation of slow wave sleep. 8,9 Early studies have shown that activation of the MT2 receptor in the retina reduces the release of dopamine, while dopamine inhibits growth cone motility and neurite outgrowth during embryonic development, 10,11 suggesting the involvement of the MT2 receptor in functional axonogenesis. In mutant mice with deficient expression of the MT2 gene, the induction of long-term potentiation (LTP) of excitatory synaptic transmission is impaired, and this impairment is closely related to deficits in learning. 12 In the hippocampus, the MT2 receptor inhibits GABA A receptor-mediated current, 13 which is implicated in the synaptic transmission. In Alzheimer's disease, expression of the MT...

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“…Thus, a substantial number of different molecules are activated by different mechanisms in neurons after injury. They are all of importance for the survival of neurons and particularly for redirection to the production of substances needed for nerve regeneration (Abe & Cavalli, 2008;Raivich & Makwana, 2007;Rossi, Gianola, & Corvetti, 2007).…”

Section: The Intrinsic Response In Neurons and Schwann Cells After Inmentioning

confidence: 99%

The Role of Timing in Nerve Reconstruction

Dahlin

2013

International Review of Neurobiology

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The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them.In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in non-neuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point towards the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury.

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Regulation of intrinsic neuronal properties for axon growth and regeneration

Cited by 134 publications

References 360 publications

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling

The Role of Timing in Nerve Reconstruction

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