Vascular Endothelial Growth Factor (VEGF) Prevents the Downregulation of the Cholinergic Phenotype in Axotomized Motoneurons of the Adult Rat

Vascular endothelial growth factor (VEGF) was initially characterized by its activity on the vascular system. However, there is growing evidence indicating that VEGF also acts as a neuroprotective factor, and that its administration to neurons suffering from trauma or disease is able to rescue them from cell death. We questioned whether VEGF could also maintain damaged neurons in a neurotransmissive mode by evaluating the synthesis of their neurotransmitter, and whether its action would be direct or through its well-known angiogenic activity. Adult rat extraocular motoneurons were chosen as the experimental model. Lesion was performed by monocular enucleation and immediately a gelatine sponge soaked in VEGF was implanted intraorbitally. After 7 days, abducens, trochlear, and oculomotor nuclei were examined by immunohistochemistry against choline acetyltransferase (ChAT), the biosynthetic enzyme of the motoneuronal neurotransmitter acetylcholine. Lesioned motoneurons exhibited a noticeable ChAT downregulation which was prevented by VEGF administration. To explore whether this action was mediated via an increase in blood vessels or in their permeability, we performed immunohistochemistry against laminin, glucose transporter-1 and the plasmatic protein albumin. The quantification of the immunolabeling intensity against these three proteins showed no significant differences between VEGF-treated, axotomized and control animals. Therefore, the present data indicate that VEGF is able to sustain the cholinergic phenotype in damaged motoneurons, which is a first step for adequate neuromuscular neurotransmission, and that this action seems to be mediated directly on neurons since no sign of angiogenic activity was evident. These data reinforces the therapeutical potential of VEGF in motoneuronal diseases.España, MINECO and FEDER BFU2015-64515-PJunta de Andalucía and FEDER : P10-CVI605

Particle Swarm Optimisation Prediction Model for Surface Roughness

Acrylic sheet is a crystal clear (with transparency equal to optical glass), lightweight material having outstanding weather ability, high impact resistance, good chemical resistance, and excellent thermo-formability and machinability. This paper develops the artificial intelligent model using partial swarm optimization (PSO) to predict the optimum surface roughness when cutting acrylic sheets with laser beam cutting (LBC). Response surface method (RSM) was used to minimize the number of experiments. The effect of cutting speed, material thickness, gap of tip and power towards surface roughness were investigated. It was found that the surface roughness is significantly affected by the tip distance followed by the power requirement, cutting speed and material thickness. Surface roughness becomes larger when using low power, tip distance and material thickness. Combination of low cutting speed, high power, tip distance and material distance produce fine surface roughness. Some defects were found in microstructure such as burning, melting and wavy surface. The optimized parameters by PSO are cutting speed (2600 pulse/s), tip distance (9.70 mm), power (95%) and material thickness (9 mm) which produce roughness around 0.0129 µm

Interaction of Both Positive and Negative Daily-Life Experiences with FKBP5 Haplotype on Psychosis Risk.

Background: There is limited research on the interaction of both positive and negative daily-life environments with stress-related genetic variants on psychotic experiences (PEs) and negative affect (NA) across the extended psychosis phenotype. This study examined whether the FK506 binding protein 51 (FKBP5) variability moderates the association of positive and negative experiences in the moment with PEs and NA in participants with incipient psychosis and their nonclinical counterparts. Methods: A total of 233 nonclinical and 86 incipient psychosis participants were prompted for a 1-week period to assess their day-to-day experiences. Participants were genotyped for four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080). Results: Multilevel analyses indicated that, unlike the risk haplotype, the protective FKBP5 haplotype moderated all the associations of positive experiences with diminished PEs and NA in incipient psychosis compared with nonclinical group. Conclusions: Participants with incipient psychosis showed symptomatic improvement when reporting positive appraisals in the interpersonal domain, which suggests that these act as a powerful coping mechanism. The fact that this occurred in daily-life underscores the clinical significance of this finding and pinpoints the importance of identifying protective mechanisms. In addition, results seem to concur with the vantage sensitivity model of gene-environment interaction, which poses that certain genetic variants may enhance the likelihood of benefiting from positive exposures

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Target-derived neurotrophins exert powerful synaptotrophic actions in the adult brain and are involved in the regulation of different forms of synaptic plasticity. Target disconnection produces a profound synaptic stripping due to the lack of trophic support. Conse- quently, target reinnervation leads to synaptic remodeling and restoration of cellular functions. Extraocular motoneurons are unique in that they normally express the TrkA neurotrophin receptor in the adult, a feature not seen in other cranial or spinal motoneurons, except after lesions such as axotomy or in neurodegenerative diseases like amyotrophic lateral sclerosis. We investigated the effects of nerve growth factor (NGF) by retrogradely delivering this neurotrophin to abducens motoneurons of adult cats. Axotomy reduced the density of somatic boutons and the overall tonic and phasic firing modulation. Treatment with NGF restored synaptic inputs and firing modu- lation in axotomized motoneurons. When K252a, a selective inhibitor of tyrosine kinase activity, was applied to specifically test TrkA effects, the NGF-mediated restoration of synapses and firing-related parameters was abolished. Discharge variability and recruitment threshold were, however, increased by NGF compared with control or axotomized motoneurons. Interestingly, these parameters re- turned to normal following application of REX, an antibody raised against neurotrophin receptor p75 (p75 NTR). In conclusion, NGF, acting retrogradely through TrkA receptors, supports afferent boutons and regulates the burst and tonic signals correlated with eye movements. On the other hand, p75 NTR activation regulates recruitment threshold, which impacts on firing regularity. To our knowledge, this is the first report showing powerful synaptotrophic effects of NGF on motoneurons in vivo

Functional Diversity of Neurotrophin Actions on the Oculomotor System

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF, BDNF or NT-3 protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT. In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review we summarize these evidences and discuss them in the context of other motor systems.Ministerio de Economía y Competitividad FEDER BFU2009-07121, BFU2012-33975, BFU2015-64515-PJunta de Andalucía-FEDER CVI-605

Extraocular motoneurons of the adult rat show higher levels of vascular endothelial growth factor and its receptor Flk-1 than other cranial motoneurons

Recent studies show a relationship between the deficit of vascular endothelial growth factor (VEGF) and motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). VEGF delivery protects motoneurons from cell death and delayed neurodegeneration in animal models of ALS. Strikingly, extraocular motoneurons show lesser vulnerability to neurodegeneration in ALS compared to other cranial or spinal motoneurons. Therefore, the present study investigates possible differences in VEGF and its main receptor VEGFR-2 or Flk-1 between extraocular and non-extraocular brainstem motoneurons. We performed immunohistochemistry and Western blot to determine the presence of VEGF and Flk-1 in rat motoneurons located in the three extraocular motor nuclei (abducens, trochlear and oculomotor) and to compare it to that observed in two other brainstem nuclei (hypoglossal and facial) that are vulnerable to degeneration. Extraocular motoneurons presented higher amounts of VEGF and its receptor Flk-1 than other brainstem motoneurons, and thus these molecules could be participating in their higher resistance to neurodegeneration. In conclusion, we hypothesize that differences in VEGF availability and signaling could be a contributing factor to the different susceptibility of extraocular motoneurons, when compared with other motoneurons, in neurodegenerative diseases

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Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When Compared with Other Brainstem Motor Systems

Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons. In brainstem samples, brain-derived neurotrophic factor was present both in extraocular and facial motoneuron somata, and to a lesser degree, in hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei, while facial and hypoglossal motoneurons were almost devoid of this protein. Finally, nerve growth factor was not present in the soma of any group of motoneurons, although it was present in dendrites of motoneurons located in the neuropil. Neuropil optical density levels were higher in extraocular motoneuron nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be originated in target muscles, since Western blot analyses revealed the presence of the three molecules in all sampled muscles, to a larger extent in extraocular muscles when compared with facial and tongue muscles. We suggest that the different neurotrophin availability could be related to the particular resistance of extraocular motoneurons to neurodegeneration.MINECO BFU2012-33975MINECO BFU2015-64515-P

Prediction equations of skinfold in children of primary school

El objetivo de este trabajo es crear ecuaciones que estimen las medidas de los pliegues cutáneos para escolares de 6 a 13 años de edad. Como resultado se obtuvieron catorce ecuaciones que estiman algunos pliegues cutáneos. Las ecuaciones se validaron con muestras aleatorias de 479 niñas y 541 niños del estado de Puebla y otras 2 muestras aleatorias del estado de Veracruz con 155 niñas y 146 niños respectivamente; las mediciones directas se realizaron con la metodología y unidades ISAK (International Society for the Advancement of Kinanthropometry)The aim of this paper is to create equations that predict the skinfold measures for school children 6 to 13 years old. Fourteen resulting equations were derived to estimate some measures of skinfold. The equations were validated with random samples of 479 girls and 541 boys in the state of Puebla and 2 other random samples of the state of Veracruz with 155 girls and 146 boys respectively; direct measurements were performed with the methodology and units ISAK (International Society for the Advancement of Kinanthropometr

Neural Progenitor Cell Implants in the Lesioned Medial Longitudinal Fascicle of Adult Cats Regulate Synaptic Composition and Firing Properties of Abducens Internuclear Neurons

Transplants of neural progenitor cells (NPCs) into the injured CNS have been proposed as a powerful tool for brain repair, but, to date, few studies on the physiological response of host neurons have been reported. Therefore, we explored the effects of NPC implants on the discharge characteristics and synaptology of axotomized abducens internuclear neurons, which mediate gaze conjugacy for horizontal eye movements. NPCs were isolated from the subventricular zone of neonatal cats and implanted at the site of transection in the medial longitudinal fascicle of adult cats. Abducens internuclear neurons of host animals showed a complete restoration of axotomy-induced alterations in eye position sensitivity, but eye velocity sensitivity was only partially regained. Analysis of the inhibitory and excitatory components of the discharge revealed a normal re-establishment of inhibitory inputs, but only partial re-establishment of excitatory inputs. Moreover, their inhibitory terminal coverage was similar to that in controls, indicating that there was ultimately no loss of inhibitory synaptic inputs. Somatic coverage by synaptophysin-positive contacts, however, showed intermediate values between control animals and animals that had undergone axotomy, likely due to partial loss of excitatory inputs. We also demonstrated that severed axons synaptically contacted NPCs, most of which were VEGF immunopositive, and that abducens internuclear neurons expressed the VEGF receptor Flk1. Together, our results suggest that VEGF neurotrophic support might underlie the increased inhibitory-to-excitatory balance observed in the postimplant cells. The noteworthy improvement of firing properties of injured neurons following NPC implants indicates that these cells might provide a promising therapeutic strategy after neuronal lesions