Nicotine-induced plasticity in the retinocollicular pathway: Evidence for involvement of amyloid precursor protein

Gonçalves, Renata Guedes de Jesus; Vasques, Juliana Ferreira; Trindade, Pablo; Serfaty, Claudio Alberto; Campello-Costa, Paula; Faria-Melibeu, Adriana da Cunha

doi:10.1016/j.neuroscience.2015.11.031

Cited by 7 publications

(7 citation statements)

References 61 publications

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“…Several mechanisms coordinate the formation, stabilization, and maintenance of retinal afferents within target [14][15][16]. Recently, we demonstrated that intravitreous injection with either IL-2 or IL-6 leads to a reorganization of retinotectal axons [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…During this period (PND10 to PND14), retinal activity that instructs the formation of retinotectal map is driven by cholinergic, and then glutamatergic activity [16]. In the retina, IL-4 exerts a modulatory effect on the cholinergic system [32] and an imbalance in cholinergic activity disrupts the retinotectal topography [14,16]. Therefore, it is possible to postulate that IL-4 modulates this activity, and, as a consequence, the distribution of retinal axons in the SC.…”

Section: Discussionmentioning

confidence: 99%

“…During development, retinal afferents undergo, within the first 2-3 postnatal weeks [11,12], an active remodeling in the superior colliculus (SC) supported by several molecular and activity-dependent mechanisms [13][14][15]. These activity-dependent mechanisms include the spontaneous firing of retinal ganglion cells in the retina mediated by either cholinergic (until postnatal day 11 [PND11]) or glutamatergic (until PND14) transmission, followed by light-evoked glutamatergic activity after eye-opening [16].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Goulart¹,

Menezes²,

Espírito-Santo³

et al. 2018

Neuroimmunomodulation

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Objective: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC). Material and Methods: Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons. Results: Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups. Conclusions: These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Goulart¹,

Menezes²,

Espírito-Santo³

et al. 2018

Neuroimmunomodulation

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“…120‐μm‐thick slices were obtained using a cryostat. Rats were submitted to intracranial implant of either GI254023X or vehicle‐loaded Elvax at PND 7 as described by Gonçalves et al (2016). At PND 10 elvax‐implanted animals were then submitted to ME.…”

Section: Methodsmentioning

confidence: 99%

“…For biochemical assays, samples were obtained and processed as previously described (Tavares Gomes et al, 2009;Mendonç a et al, 2010;Trindade et al, 2011;Gonç alves et al, 2016). Briefly, rats were deeply anaesthetized by isoflurane inhalation and decapitated.…”

Section: Western Blottingmentioning

confidence: 99%

Monocular denervation of visual nuclei modulates APP processing and sAPPα production: A possible role on neural plasticity

Vasques

Heringer

Gonçalves

et al. 2017

Intl J of Devlp Neuroscience

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Amyloid precursor protein (APP) is essential to physiological processes such as synapse formation and neural plasticity. Sequential proteolysis of APP by beta- and gamma-secretases generates amyloid-beta peptide (Aβ), the main component of senile plaques in Alzheimer Disease. Alternative APP cleavage by alpha-secretase occurs within Aβ domain, releasing soluble α-APP (sAPPα), a neurotrophic fragment. Among other functions, sAPPα is important to synaptogenesis, neural survival and axonal growth. APP and sAPPα levels are increased in models of neuroplasticity, which suggests an important role for APP and its metabolites, especially sAPPα, in the rearranging brain. In this work we analyzed the effects of monocular enucleation (ME), a classical model of lesion-induced plasticity, upon APP content, processing and also in secretases levels. Besides, we addressed whether α-secretase activity is crucial for retinotectal remodeling after ME. Our results showed that ME induced a transient reduction in total APP content. We also detected an increase in α-secretase expression and in sAPP production concomitant with a reduction in Aβ and β-secretase contents. These data suggest that ME facilitates APP processing by the non-amyloidogenic pathway, increasing sAPPα levels. Indeed, the pharmacological inhibition of α-secretase activity reduced the axonal sprouting of ipsilateral retinocollicular projections from the intact eye after ME, suggesting that sAPPα is necessary for synaptic structural rearrangement. Understanding how APP processing is regulated under lesion conditions may provide new insights into APP physiological role on neural plasticity.

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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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Nicotine-induced plasticity in the retinocollicular pathway: Evidence for involvement of amyloid precursor protein

Cited by 7 publications

References 61 publications

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Monocular denervation of visual nuclei modulates APP processing and sAPPα production: A possible role on neural plasticity

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

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