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ProNGF derived from rat sciatic nerves downregulates neurite elongation and axon specification in PC12 cells

Overview of attention for article published in Frontiers in Cellular Neuroscience, September 2015
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Title
ProNGF derived from rat sciatic nerves downregulates neurite elongation and axon specification in PC12 cells
Published in
Frontiers in Cellular Neuroscience, September 2015
DOI 10.3389/fncel.2015.00364
Pubmed ID
Authors

Anna Sofía Trigos, Marines Longart, Lisbeth García, Cecilia Castillo, Patricia Forsyth, Rafael Medina

Abstract

Several reports have shown that a sciatic nerve conditioned media (CM) causes neuronal-like differentiation in PC12 cells. This differentiation is featured by neurite outgrowth, which are exclusively dendrites, without axon or sodium current induction. In previous studies, our group reported that the CM supplemented with a generic inhibitor for tyrosine kinase receptors (k252a) enhanced the CM-induced morphological differentiation upregulating neurite outgrowth, axonal formation and sodium current elicitation. Sodium currents were also induced by depletion of endogenous precursor of nerve growth factorr (proNGF) from the CM (pNGFd-CM). Given that sodium currents, neurite outgrowth and axon specification are important features of neuronal differentiation, in the current manuscript, first we investigated if proNGF was hindering the full PC12 cell neuronal-like differentiation. Second, we studied the effects of exogenous wild type (pNGFwt) and mutated (pNGFmut) proNGF isoforms over sodium currents and whether or not their addition to the pNGFd-CM would prevent sodium current elicitation. Third, we investigated if proNGF was exerting its negative regulation through the sortilin receptor, and for this, the proNGF action was blocked with neurotensin (NT), a factor known to compete with proNGF for sortilin. Thereby, here we show that pNGFd-CM enhanced cell differentiation, cell proportion with long neurites, total neurite length, induced axonal formation and sodium current elicitation. Interestingly, treatment of PC12 cells with wild type or mutated proNGF isoforms elicited sodium currents. Supplementing pNGFd-CM with pNGFmut reduced 35% the sodium currents. On the other hand, pNGFd-CM+pNGFwt induced larger sodium currents than pNGFd-CM. Finally, treatments with CM supplemented with NT showed that sortilin was mediating proNGF negative regulation, since its blocking induced similar effects than the pNGFd-CM treatment. Altogether, our results suggest that proNGF within the CM, is one of the main inhibitors of full neuronal differentiation, acting through sortilin receptor.

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Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 43%
Student > Bachelor 1 14%
Other 1 14%
Student > Master 1 14%
Unknown 1 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 43%
Biochemistry, Genetics and Molecular Biology 1 14%
Neuroscience 1 14%
Unknown 2 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 September 2015.
All research outputs
#18,317,556
of 23,538,320 outputs
Outputs from Frontiers in Cellular Neuroscience
#3,052
of 4,374 outputs
Outputs of similar age
#183,213
of 270,246 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#96
of 139 outputs
Altmetric has tracked 23,538,320 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,374 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
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We're also able to compare this research output to 139 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.