Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.

The intra-axonal events governing formation of presynaptic terminals are still poorly understood. Pinto et al. reveal a mechanism by which a localized decrease in proteasome degradation and resultant accumulation of polyubiquitinated proteins at nascent sites signal assembly of presynaptic terminals.

SUMMARY Ribosomes and a subset of cellular mRNAs are trafficked into axons of developing neurons. The axonal localization of translational machinery allows new proteins to be rapidly and locally synthesized during axonal growth and pathfinding. However, in mature neurons, axonal ribosomes are significantly reduced or even absent. The mechanism that elicits this removal is currently unknown. Here, we demonstrate that synapse formation is the trigger for ribosome reduction in mature axons. In vivo analysis shows that axonal ribosome levels decrease in rat brain at a developmental stage coincident with synapse formation. Next, we observe in vitro that different synaptogenic inducers trigger an overall decrease of ribosomal proteins and rRNA in the axons of spinal motor neurons. We further observe that this process is dependent on the ubiquitin-proteasome system but not on autophagy. Together, these data identify synaptogenesis as the long missing biological trigger that leads to ribosome disappearance during axonal maturation.

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The neurotrophin brain‐derived neurotrophic factor (BDNF) plays multiple roles in the nervous system, including in neuronal development, in long‐term synaptic potentiation in different brain regions, and in neuronal survival. Alterations in these regulatory mechanisms account for several diseases of the nervous system. The synaptic effects of BDNF mediated by activation of tropomyosin receptor kinase B (TrkB) receptors are partly mediated by stimulation of local protein synthesis which is now considered a ubiquitous feature in both presynaptic and postsynaptic compartments of the neuron. The capacity to locally synthesize proteins is of great relevance at several neuronal developmental stages, including during neurite development, synapse formation, and stabilization. The available evidence shows that the effects of BDNF–TrkB signaling on local protein synthesis regulate the structure and function of the developing and mature synapses. While a large number of studies have illustrated a wide range of effects of BDNF on the postsynaptic proteome, a growing number of studies also point to presynaptic effects of the neurotrophin in the local regulation of the protein composition at the presynaptic level. Here, we will review the latest evidence on the role of BDNF in local protein synthesis, comparing the effects on the presynaptic and postsynaptic compartments. Additionally, we overview the relevance of BDNF‐associated local protein synthesis in neuronal development and synaptic plasticity, at the presynaptic and postsynaptic compartments, and their relevance in terms of disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications RNA Export and Localization > RNA Localization

ClearPEM is a rotating, dual planar detector PET system dedicated to breast and axilla imaging that needs data corrections in order to improve quantification and lesion detectability. Since the scanner does not have CT nor transmission sources, we are implementing data corrections that use emission-only data. Also, since in this work we are using an iterative list-mode reconstruction algorithm that projects the data directly through a 3D grid of points, all the corrections are applied in image space. We describe the current implementation and validation of image-based corrections for normalization, scatter, attenuation and randoms. Normalization correction uses sensitivity images generated by backprojecting data from a planar source. Energy-based scatter correction is applied using the Estimation of Trues Method because this method does not require information about attenuating media and takes into account the activity outside the FOV. Attenuation correction is calculated from the segmentation of the breast in the emission images. Randoms correction is performed by subtraction of a smoothed image obtained from the backprojection of the delayed coincidences. The implementation of other corrections is also being pursued in order to obtain fully quantitative images in breast imaging.

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