Rapid plasticity of intact axons following a lesion to the visual pathways during early brain development is triggered by microglial activation

Chagas, Luana da Silva; Trindade, Pablo; Tavares-Gomes, Ana Lúcia; Mendonça, Henrique Rocha; Campello-Costa, Paula; Faria-Melibeu, Adriana da Cunha; Linden, Rafael; Serfaty, Claudio Alberto

doi:10.1016/j.expneurol.2018.10.002

Cited by 14 publications

(15 citation statements)

References 69 publications

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“…In addition, the use of pharmacological blockers of microglial activation, cyclosporine A (CsA) (or minocycline), prevented microglial activation and axonal plasticity in this system ( Figure 2). The same result was obtained after the local administration of a TNF-α neutralizing antibody, supporting that an inflammatory context soon after injury is a necessary condition for the promotion of adaptive plasticity and structural remodeling responses of the neural circuits, enabling a rapid recovery of the system in the early stages of development [77]. Following a monocular enucleation at P10, an extensive contralateral SC denervation occurs, followed by rapid compensatory growth of the axons from the intact eye.…”

Section: Neuroinflammation and Microglial Function In Lesion Recoverysupporting

confidence: 62%

“…Microglial activation begins with an increase in cell numbers, displaying an ameboid profile within 24 h (Figure 2), followed by a peak in the microglial colonization 3 days after the lesion. The reestablishment of the morphological profile, similar to the uninjured animals, occurred 7 days after the lesion [77]. In addition, the use of pharmacological blockers of microglial activation, cyclosporine A (CsA) (or minocycline), prevented microglial activation and axonal plasticity in this system ( Figure 2).…”

Section: Neuroinflammation and Microglial Function In Lesion Recoverymentioning

confidence: 90%

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Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Chagas

Sandre

Ribeiro

et al. 2020

IJMS

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Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial-immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre-and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

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Section: Neuroinflammation and Microglial Function In Lesion Recoverysupporting

confidence: 62%

Section: Neuroinflammation and Microglial Function In Lesion Recoverymentioning

confidence: 90%

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Chagas

Sandre

Ribeiro

et al. 2020

IJMS

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“…M2 activated microglia are anti-inflammatory and neuroprotective, secreting neurotrophic factor and promoting axon regeneration. For example, microglia have been shown to encourage axon elongation and presynaptic site formation following pyramidal tract section (Jiang et al, 2019) as well as promote plasticity following lesions within the visual pathways (Chagas et al, 2019). However, this binary system represents an oversimplification of microglial function.…”

Section: Modulating Glial Cell-axonal Growth Cone Interactions To Aidmentioning

confidence: 99%

Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

2020

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The developing nervous system is a complex yet organized system of neurons, glial support cells, and extracellular matrix that arranges into an elegant, highly structured network. The extracellular and intracellular events that guide axons to their target locations have been well characterized in many regions of the developing nervous system. However, despite extensive work, we have a poor understanding of how axonal growth cones interact with surrounding glial cells to regulate network assembly. Gliato-growth cone communication is either direct through cellular contacts or indirect through modulation of the local microenvironment via the secretion of factors or signaling molecules. Microglia, oligodendrocytes, astrocytes, Schwann cells, neural progenitor cells, and olfactory ensheathing cells have all been demonstrated to directly impact axon growth and guidance. Expanding our understanding of how different glial cell types directly interact with growing axons throughout neurodevelopment will inform basic and clinical neuroscientists. For example, identifying the key cellular players beyond the axonal growth cone itself may provide translational clues to develop therapeutic interventions to modulate neuron growth during development or regeneration following injury. This review will provide an overview of the current knowledge about glial involvement in development of the nervous system, specifically focusing on how glia directly interact with growing and maturing axons to influence neuronal connectivity. This focus will be applied to the clinically-relevant field of regeneration following spinal cord injury, highlighting how a better understanding of the roles of glia in neurodevelopment can inform strategies to improve axon regeneration after injury.

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“…No significant increase was detected in the following analyzed survival points, at 48 hr (105.2 ± 7.31), 72 hr (109.2 ± 5.02), and 1 week (115.2 ± 10.39) after ME (Figure 3). Interestingly, the increase in ERK phosphorylation coincides with the peak of plastic response induced by ME performed at PND10 (Chagas et al., 2019), indicating that this signaling pathway possibly plays a critical role in the initial stages of axonal restructuring of ipsilateral projections in deafferented SC.…”

Section: Resultsmentioning

confidence: 91%

“…Microgliosis and astrogliosis are elicited in SC after ME (Wilm & Bahr, 1995). Recently, our group described that treatment with microglial inhibitors block the structural reorganization induced by ME (Chagas et al., 2019). Therefore, the role of glial cells in neuroplasticity cannot be disregarded.…”

Section: Discussionmentioning

confidence: 99%

Signaling pathways modulated by monocular enucleation in the superior colliculus of juvenile rats

Vasques

Gonçalves

Tavares-Gomes

et al. 2021

Intl J of Devlp Neuroscience

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Monocular eye enucleation (ME) is a classical paradigm to induce neural plasticity in retinal ganglion cells (RGCs) axons from the intact eye, especially when performed within the critical period of visual system development. However, the precise mechanisms underlying the axonal sprouting and synaptogenesis seen in this model remain poorly understood. In the present work, we investigated the temporal alterations in phosphorylation of three kinases related to axonal growth and synaptogenesis—GSK3β (an important repressor of axonal outgrowth), AKT, and ERK—in superior colliculus of rats submitted to ME during early postnatal development. Western blotting analysis showed an increase in pGSK3β, the inactive form of this enzyme, 24 and 48 hr after ME. Accordingly, an increase in pERK levels was detected 24 hr after ME, indicating that phosphorylation of these enzymes might be related to axonal reorganization induced by ME. Interestingly, AKT phosphorylation was increased just 1 week after ME, suggesting it may be involved in the stabilization of newly formed synapses, rising from the axonal reorganization of remaining eye. A better understanding of how signaling pathways are modulated in a model of intense axonal sprouting can highlight possible therapeutic targets in RGCs injuries in adult individuals, where axonal regrowth is nearly absent.

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Rapid plasticity of intact axons following a lesion to the visual pathways during early brain development is triggered by microglial activation

Cited by 14 publications

References 69 publications

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

Signaling pathways modulated by monocular enucleation in the superior colliculus of juvenile rats

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