Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth

Quintá, Héctor Ramiro; Wilson, Carlos Pizarro; Blidner, Ada G.; González-Billault, Christian; Pasquini, Laura; Rabinovich, Gabriel A.; Pasquini, Juana M.

doi:10.1016/j.expneurol.2016.06.009

Cited by 21 publications

(24 citation statements)

References 49 publications

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“…These observations are in line with our previous results in regenerating spinal axons (Quinta et al, , ), where we have identified the mechanism underling exogenous Gal‐1 promotion of axonal re‐growth after SCI and concomitant recovery of locomotor activity. Interestingly this process only occurs when Gal‐1 acquires its dimeric conformation.…”

Section: Discussionsupporting

confidence: 93%

“…The present results constitute strong evidence against a role of endogenous galectin on axonal development in the spinal cord; discarding the presence of alterations in the neuronal architecture, as well as in the locomotor behavior provoked by the lack of endogenous Gal‐1. In this context, our results provide additional support to studies using lgals‐1 ‐/‐ mice models of SCI or traumatic brain injury (Quinta et al, , ; Sirko et al, ). Furthermore, they will allow to extend the investigation on the neuro‐regenerative properties of dimeric Gal‐1 treatment in these traumatic pathologies and potentially other pathologies in the CNS.…”

Section: Discussionsupporting

confidence: 84%

“…Developing motor and commissural axons were demonstrated using a mouse monoclonal anti‐Neurofilament‐M (NFM) antibody raised against whole rat NFM protein (Invitrogen, USA; Cat. 13–0700; RRID: AB_2532998), (Lee, Carden, Schlaepfer, & Trojanowski, ; Quinta et al, , ). Sensory axons were immunostained with mouse monoclonal anti peripherin antibody.…”

Section: Methodsmentioning

confidence: 99%

“…Sensory axons were immunostained with mouse monoclonal anti peripherin antibody. The antibody was raised against the 4 N‐terminal aminoacids of rat peripherin protein (Millipore, USA; Cat MAB1527; RRID: AB_2284441), (Sommer, Shah, Rao, & Anderson, ; Quinta et al, ). Adult tissue samples were stained for GFAP and βIII‐tubulin (neuronal) for histological analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Ab39350; RRID: AB_944890), (Gutekunst, Stewart, Franz, English, & Gross, ). The specificity of the anti‐PlexinA4 antibody has been further characterized in our laboratory by western blot analysis and immunofluorescence (Quinta et al, , ). Gal‐1 was demonstrated by immunohistochemistry using a rabbit polyclonal antibody generated against the N‐terminal domain of human Gal‐1 (aminoacids 1–45), (Santa Cruz, USA; Cat.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL‐1

Pasquini

Barrantes

Quintá

2017

J of Comparative Neurology

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It was recently described that Galectin-1 (Gal-1) promotes axonal growth after spinal cord injury. This effect depends on protein dimerization, since monomeric Gal-1 fails to stimulate axonal re-growth. Gal-1 is expressed in vivo at concentrations that favor the monomeric species. The aim of the present study is to investigate whether endogenous Gal-1 is required for spinal axon development and normal locomotor behavior in mice. In order to characterize axonal development, we used a novel combination of 3-DISCO technique with 1-photon microscopy and epifluorescence microscopy under high power LED illumination, followed by serial image section deconvolution and 3-D reconstruction. Cleared whole lgals-1 embryos were used to analyze the 3-D cytoarchitecture of motor, commissural, and sensory axons. This approach allowed us to evaluate axonal development, including the number of fibers, fluorescence density of the fiber tracts, fiber length as well as the morphology of axonal sprouting, deep within the tissue. Gal-1 deficient embryos did not show morphological/anatomical alterations in any of the axonal populations and parameters analyzed. In addition, specific guidance receptor PlexinA4 did not change its axonal localization in the absence of Gal-1. Finally, Gal-1 deficiency did not change normal locomotor activity in post-natal animals. Taken together, our results show that development of spinal axons as well as the locomotor abilities observed in adult mice are independent of Gal-1. Supporting our previous observations, the present study further validates the use of lgals-1 mice to develop spinal cord- or traumatic brain injury models for the evaluation of the regenerative action of Gal-1.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL‐1

Pasquini

Barrantes

Quintá

2017

J of Comparative Neurology

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Transplantation of Olfactory Stem Cells with Biodegradable Hydrogel Accelerates Facial Nerve Regeneration After Crush Injury

Esaki

Katsumi

Hamajima

et al. 2018

Stem Cells Translational Medicine

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Olfactory mucosa contains neural stem cells, called olfactory stem cells (OSCs), which produce trophic support required for promoting axonal regeneration after nerve injury. However, the local tissue environment can reduce the viability/function of transplanted cells when placed directly on the injury. Although gelatin hydrogels have been shown to aid cell survival during transplantation, such OSC‐hydrogel combinations have not been extensively tested, particularly during recovery from facial nerve palsy. In this study, OSCs were isolated from the olfactory mucosae of newborn mice and were shown to express neural stem cell markers before differentiation, as well as cell‐type specific markers after differentiation, confirming their multipotency. The OSCs also secrete growth factors and various cytokines that promote nerve regeneration. To test the effects of OSC transplantation in vivo, Medgel, a biodegradable hydrogel sponge, was applied to retain OSCs around the injury site and to lessen the detrimental effects of the local environment in an established facial nerve palsy mouse model. When OSCs were transplanted into the injury site, accelerated recovery was observed for 1 week. When OSCs were transplanted with Medgel, a higher level and duration of accelerated recovery was observed. OSCs in Medgel also increased peripheral nerve function and increased the number of regenerated nerve fibers. These results suggest that OSCs implanted with Medgel accelerate and enhance recovery from facial palsy in mice. Because human OSCs can be easily obtained from olfactory mucosa biopsies with limited risk, this OSC‐Medgel combination is a candidate treatment option for accelerating recovery after facial nerve injury. stem cells translational medicine 2019;8:169&10

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Redox regulation in regenerative medicine and tissue engineering: The paradox of oxygen

Sthijns

Blitterswijk

LaPointe

2018

J Tissue Eng Regen Med

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One of the biggest challenges in tissue engineering and regenerative medicine is to incorporate a functioning vasculature to overcome the consequences of a lack of oxygen and nutrients in the tissue construct. Otherwise, decreased oxygen tension leads to incomplete metabolism and the formation of the so‐called reactive oxygen species (ROS). Cells have many endogenous antioxidant systems to ensure a balance between ROS and antioxidants, but if this balance is disrupted by factors such as high levels of ROS due to long‐term hypoxia, there will be tissue damage and dysfunction. Current attempts to solve the oxygen problem in the field rarely take into account the importance of the redox balance and are instead centred on releasing or generating oxygen. The first problem with this approach is that although oxygen is necessary for life, it is paradoxically also a highly toxic molecule. Furthermore, although some oxygen‐generating biomaterials produce oxygen, they also generate hydrogen peroxide, a ROS, as an intermediate product. In this review, we discuss why it would be a superior strategy to supplement oxygen delivery with molecules to safeguard the important redox balance. Redox sensor proteins that can stimulate the anaerobic metabolism, angiogenesis, and enhancement of endogenous antioxidant systems are discussed as promising targets. We propose that redox regulating biomaterials have the potential to tackle some of the challenges related to angiogenesis and that the knowledge in this review will help scientists in tissue engineering and regenerative medicine realize this aim.

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Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth

Cited by 21 publications

References 49 publications

Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL‐1

Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL‐1

Transplantation of Olfactory Stem Cells with Biodegradable Hydrogel Accelerates Facial Nerve Regeneration After Crush Injury

Redox regulation in regenerative medicine and tissue engineering: The paradox of oxygen

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