Dendritic pathology and spinal loss in the visual cortex in Alzheimer's disease: a Golgi study in pathology

Alzheimer's disease is a neurodegenerative disorder characterized by progressive decline in memory, loss of professional skills, impairment of judgement and behavior, and decline in social performances. In terms of neuropathology, the morphological hallmarks of the disease are the accumulation of alpha-beta peptide and the neurofibrillary degeneration, associated with synaptic alterations, involving mostly the dendritic spines. This study is based on the morphological analysis of 10 brains, 5 of which were obtained from patients who suffered from Alzheimer's disease and 5 from nondemented senile individuals used as control group. The segments taken in major from the occipital lobe were studied with the use of Golgi method, as well as Gallyas' and Bielschowski' s staining methods. In most of the pyramidal cells in the affected brains, there seems to be important spine loss and extensive dendrite pathology. Apical dendrites are distorted and tortuous. Horizontal dendritic arborization is severely decreased leading to an amputated, bell-shaped cell soma. Senile plaques have been often revealed, and neurofibrillary changes have also been noticed.     

Evaluation of the Protection Ability of a Magnesium Hydroxide Coating against the Bio-Corrosion of Concrete Sewer Pipes,by Using Short and Long Duration Accelerated Acid Spraying Tests

The Microbiologically Induced Corrosion (MIC) of concrete sewer pipes is a commonly known problem that can lead to the destruction of the system, creating multiple public health issues and the need for costly repair investments. The present study focuses on the development of a magnesium hydroxide coating, with optimized properties to protect concrete against MIC. The anti-corrosion properties of the respective coating were evaluated by using short and long duration accelerated sulfuric acid spraying tests. The coating presented satisfying adhesion ability, based on pull-off and Scanning Electron Microscopy (SEM) analysis measurements. The surface pH of the coated concrete was maintained at the alkaline region (i.e., >8.0) throughout the duration of all acid spraying tests. The consumption of the coating, due to the reaction (neutralization) with sulfuric acid, was confirmed by the respective mass and thickness measurements. The protection ability of this coating was also evaluated by recording the formation of gypsum (i.e., the main corrosion product of concrete) during the performed tests, by X-ray Diffraction (XRD) analysis and by the Attenuated Total Reflectance (ATR) measurements. Finally, a long duration acid spraying test was additionally used to evaluate the behavior of the coating, simulating better the conditions existing in a real sewer pipe, and the obtained results showed that this coating is capable of offering prolonged protection to the concrete substrate.     

The function of contactin‐2/TAG‐1 in oligodendrocytes in health and demyelinating pathology

The oligodendrocyte maturation process and the transition from the pre‐myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG‐1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its involvement on oligodendrocyte maturation, branching, myelin‐gene expression, myelination, and axonal function. The cuprizone model of central nervous system demyelination was further used to assess CNTN2 in pathology. During development, CNTN2 can transiently affect the expression levels of myelin and myelin‐regulating genes, while its absence results in reduced oligodendrocyte branching, hypomyelination of fiber tracts and impaired axonal conduction. In pathology, CNTN2 absence does not affect the extent of de‐ and remyelination. However during remyelination, a novel, CNTN2‐independent mechanism is revealed that is able to recluster voltage gated potassium channels (VGKCs) resulting in the improvement of fiber conduction.     

Rac1-dependent cell cycle exit of MGE precursors and GABAergic interneuron migration to the cortex

Cortical γ-aminobutyric acid (GABA)ergic interneurons are characterized by extraordinary neurochemical and functional diversity. Although recent studies have uncovered some of the molecular components underlying interneuron development, including the cellular and molecular mechanisms guiding their migration to the cortex, the intracellular components involved are still unknown. Rac1, a member of the Rac subfamily of Rho-GTPases, has been implicated in various cellular processes such as cell cycle dynamics, axonogenesis, and migration. In this study, we have addressed the specific role of Rac1 in interneuron progenitors originating in the medial ganglionic eminence, via Cre/loxP technology. We show that ablation of Rac1 from Nkx2.1-positive progenitors, results in a migratory impairment. As a consequence, only half of GABAergic interneurons are found in the postnatal cortex. The rest remain aggregated in the ventral telencephalon and show morphological defects in their growing processes in vitro. Ablation of Rac1 from postmitotic progenitors does not result in similar defects, thus underlying a novel cell autonomous and stage-specific requirement for Rac1 activity, within proliferating progenitors of cortical interneurons. Rac1 is necessary for their transition from G1 to S phase, at least in part by regulating cyclin D levels and retinoblastoma protein phosphorylation.     

Expression of the cell adhesion proteins BEN/SC1/DM-GRASP and TAG-1 defines early steps of axonogenesis in the human spinal cord

We have studied the expression pattern of two cell adhesion proteins of the immunoglobin (Ig) superfamily, BEN/SC1/DM-GRASP (BEN) and the transient axonal glycoprotein TAG-1, during the development of the human nervous system. This study was performed by immunocytochemistry on sections of human embryos ranging from 4 to 13 weeks postconception. The overall distribution of the two proteins during development is very similar to that reported in other vertebrate species, but several important differences have been observed. Both proteins exhibit a transient expression on selected neuronal populations, which include the motor and the sensory neurons. In addition, BEN was also detected on virtually all neurons derived from the neural crest as well as in nonneuronal tissues. A major difference of expression with the chick embryo is that, in the motor neurons, BEN expression was not observed at early stages of development, thus arguing against a role of this molecule in pathfinding and fasciculation. BEN was observed to be restricted to subsets of motor neurons, such as the medial column at the upper limb level. Expression was also detected in a laterodorsal population of the ventral horn cells, which are likely to correspond to migrating preganglionic neurons that originate from the motor pool at the thoracic level. TAG-1 was found on commissural neurons and weakly on the sympathetic neurons; it was also detected on restricted nonneuronal populations. In addition, we observed TAG-1 expression in fibers that could correspond either to subsets of dorsal root ganglia (DRGs) central afferences (including the Ia fibers) or to the axons of association interneurons and in scattered motoneurons likely to correspond either to preganglionic neurons, to γ-motoneurons, or to late-born motoneurons. Therefore, our results indicate that the molecular strategies used to establish the axonal scaffolding of the nervous system in humans are extremely conserved among the different vertebrates. J. Comp. Neurol. 379:415–427, 1997. © 1997 Wiley-Liss, Inc.     

Analysis of interactions of the adhesion molecule TAG-1 and its domains with other immunoglobulin superfamily members

Cell adhesion molecules of the immunoglobulin superfamily promote cell aggregation and neurite outgrowth via homophilic and heterophilic interactions. The transient axonal glycoprotein TAG-1 induces cell aggregation through homophilic interaction of its fibronectin repeats. We investigated the domains responsible for the neurite outgrowth promoting activity of TAG-1 as well as its interactions with other cell adhesion molecules. Binding experiments with Fc-chimeric proteins revealed that TAG-1 interacts with L1, NrCAM, and F3/contactin. The membrane-associated as opposed to the soluble form of TAG-1 behaves differently in these assays. We demonstrate that both the immunoglobulin as well as the fibronectin domains promote neurite outgrowth when used as substrates. Furthermore we investigated the putative role of L1 and NrCAM as the neuronal TAG-1 receptors mediating neurite extension. DRG neurons from L1-deficient mice were found to extend neurites on TAG-1 substrates and blocking NrCAM function did not diminish the TAG-1-dependent neurite outgrowth. These results indicate that neither L1 nor NrCAM are required for TAG-1-elicited neurite outgrowth.     

Alterations of juxtaparanodal domains in two rodent models of CNS demyelination

The segregation of myelinated fibers into distinct domains around the node of Ranvier—the perinodal areas—is crucial for nervous system homeostasis and efficient nerve conduction. Perinodal areas are formed by axo‐glial interactions, namely the interaction of molecules between the axon and the myelinating glia. In a variety of demyelinating pathologies including multiple sclerosis, the molecular architecture of the myelinated fiber is disrupted, leading to axonal degeneration. In this study we have analyzed the alterations of TAG‐1, Caspr2, and voltage‐gated potassium channels (VGKCs), forming the juxtaparanodal tripartite complex, in relation to adjacent paranodal and nodal molecules, in two different models of CNS demyelination, the experimental autoimmune encephalomyelitis (EAE) and the cuprizone model of toxic demyelination. We found extensive alterations of the juxtaparanodal molecular architecture under de‐ and remyelinating conditions. Inflammation alone was sufficient to disrupt the borders between the domains leading to the diffusion of juxtaparanodal components to the adjacent paranodal area. EAE induction and cuprizone‐induced demyelination resulted initially in paranodal domain elongation with subsequent diffusion of the juxtaparanodal components and the reduction of their expression levels. At later stages, with decreasing inflammation and spontaneous remyelination there was a partial restoration of the paranodal domain but not sufficient re‐organization of the juxtaparanodes. The latter were re‐formed only when complete remyelination was allowed in the cuprizone model, indicating that juxtaparanodal domain reorganization is a later event that may remain incomplete in a hostile inflammatory milieu. GLIA 2013;61:1236–1249     

Body ownership causes illusory self-attribution of speaking and influences subsequent real speaking

When we carry out an act, we typically attribute the action to ourselves, the sense of agency. Explanations for agency include conscious prior intention to act, followed by observation of the sensory consequences; brain activity that involves the feed-forward prediction of the consequences combined with rapid inverse motor prediction to fine-tune the action in real time; priming where there is, e.g., a prior command to perform the act; a cause (the intention to act) preceding the effect (the results of the action); and common-sense rules of attribution of physical causality satisfied. We describe an experiment where participants falsely attributed an act to themselves under conditions that apparently cannot be explained by these theories. A life-sized virtual body (VB) seen from the first-person perspective in 3D stereo, as if substituting the real body, was used to induce the illusion of ownership over the VB. Half of the 44 experimental participants experienced VB movements that were synchronous with their own movements (sync), and the other half asynchronous (async). The VB, seen in a mirror, spoke with corresponding lip movements, and for half of the participants this was accompanied by synchronous vibrotactile stimulation on the thyroid cartilage (Von) but this was not so for the other half. Participants experiencing sync misattributed the speaking to themselves and also shifted the fundamental frequency of their later utterances toward the stimulus voice. Von also contributed to these results. We show that these findings can be explained by current theories of agency, provided that the critical role of ownership over the VB is taken into account.There is growing evidence that the brain does not treat our body as relatively fixed, changing only slowly through time, but that its body representation demonstrates high plasticity. Although this is counter to common sense, a number of findings have shown that simple experimental manipulations can generate the illusion that an external object is part of our body (1, 2), that a plastic manikin (3, 4), and even a body displayed in immersive virtual reality (IVR), is our body (5–7). Furthermore, evidence suggests that such illusions have physiological and psychological consequences. For example, the rubber-hand illusion (RHI), where participants feel a somatic sense of ownership over a rubber hand through synchronous multisensory stimulation on the rubber and corresponding hidden real hand (1), has been shown to lead to a cooling of the real hand (8) as well as an increase in its histamine reactivity (9). The RHI over a black rubber hand can lead to a reduction of implicit racial bias in light-skinned people (10). When light-skinned people have a dark-skinned VB that apparently substitutes their own body, in IVR—as seen directly and in a virtual mirror, and that moves like themselves—they have the illusion that the body is theirs, which also results in a reduction of implicit racial bias (11). When average-sized adults have an illusion of body ownership over smaller or larger bodies, this results in changes in the perception of object sizes (12). Even more remarkably, the illusion of body ownership of adults over a virtual child body leads to overestimation of object sizes and changes in implicit attitudes about the self substantially beyond changes induced by the illusion of ownership of an adult shaped body of the same size as the child (13). Hence the type of body appears to carry with it physiological, perceptual, and even deep-seated attitudinal correlates.Following on from these findings the fundamental question in the present work is whether the factors that lead to a strong illusion of body ownership with respect to a VB would also lead to illusory agency over a specific action that was definitely not caused by participants, and where current explanations of agency apparently do not apply. “Agency” refers to the sensation of authorship of actions. Under normal circumstances humans are able to trivially distinguish their own motor actions from those of other people; we know when we are the cause of our own volitional motor actions and take responsibility for the effects. This sensation of agency has been the subject of significant study in recent years, and self-attribution of actions has been explained by a combination of feed-forward processing (we predict that we are to do an action and then observe the consequences of having carried it out) (14), with cause preceding effect, no other explanation for the result that is readily available (15), and a requirement for tight temporal binding between the intention to carry out the action and the resulting sensory consequences (16). Specific brain regions implicated in agency have been identified through the study of people with lesions (17), and although there is a significant intersection between brain activity in motor areas when observing someone else carrying out an action and when carrying it out ourselves, there are also additional processes that distinguish self-movement from others’ movement (18). Here we show that it is possible to generate an illusion of agency when apparently (i) there is no possibility of there having been feed-forward prediction, (ii) there is no thought or cause preceding the effect, and (iii) there is an obvious alternative explanation for the observed action.Our general hypothesis was that a strong illusion of ownership over a VB would map over to illusory agency with respect to an action—speaking —not executed by the participant, but only carried out by that VB. The voice that each participant heard had a higher fundamental frequency (FF) than his or her real voice. Our specific hypothesis was that a strong illusion of body ownership over the VB would result in the illusion of agency over the speaking. Moreover objective evidence of this effect would be the shift of FF of participants’ later utterances toward that of the heard voice.To study this we exploited an IVR system using a wide field-of-view (FOV) stereo head-tracked, head-mounted display (HMD) with headphones, and full-body motion-capture suit (Fig. 1A). Participants experienced a life-sized VB from a first-person perspective that was spatially coincident with and therefore substituted their own body. They saw the VB (or avatar) in a virtual mirror and when directly looking toward themselves (Fig. 1 B and C). During their experience, the VB uttered a set of prerecorded words. Our specific hypothesis was that the factors that would lead to a high level of body ownership would also result in the participants affirming that they had said the words, thus demonstrating illusory agency. Further evidence for such agency would be whether they would exhibit a shift in the FF of their voice toward that of the stimulus voice in their subsequent real utterances of the same words (19, 20).Open in a separate windowFig. 1.The experimental setup. The body of the participant was substituted by a sex-matched VB, viewed from 1PP, onto which body and head movements were mapped in real time for the sync condition. The body could also be seen as reflected in a virtual mirror. (A) Participants wore an HMD with earphones, a full-body motion-capture suit, and a vibrotactile device. (B) The female VB. (C) The male VB. B and C illustrate that the VB (here, the arms) could be seen directly when looking toward their own body, and also in the virtual mirror.We conducted the experiment with 44 participants using a between-groups design, with two binary factors referred to as visuomotor (async and sync) and vibrations (Voff and Von). In the sync condition the movements of the VB were synchronized in real time with the actual body movements of the participant. In the async condition the VB movements were generated from a prerecorded animation and independent of those of the participant. Based on past results we expected that the sync condition would result in a substantially greater illusion of body ownership over the VB than the async condition (11, 13, 21–23). The vibrations factor was designed to enhance the sense of speaking by applying vibratory feedback on the thyroid cartilage to coincide with the period that the embodied avatar was speaking (Von) or no vibratory feedback (Voff). The vibrations were synchronized with VB lip movements that were themselves synchronized with the word being said. Participants were sequentially allocated to one of the four cells of the factorial design in order of attendance to the experiment, with the final numbers as shown in Table S1, with approximate equal distribution of participants in the four cells of the experimental design and sex balance. Details are given in Materials and Methods and SI Materials and Methods and are shown in Movie S1.     

Nerve grafting in peripheral nerve microsurgery of the upper extremity

The use of microsurgical techniques is essential in peripheral nerve surgery, in which dissection at the fascicular level is required. Magnification with an operating microscope allows for an accurate evaluation of the severity of the trauma to the nerve tissue and permits atraumatic interfascicular dissection. Fascicular or interfascicular dissection and repair with the use of nerve grafts was carried out in 220 peripheral nerve lesions of the upper extremity. Our results of nerve-grafting in the upper extremity (median, ulnar, and radial-nerves) indicate an inverse association between the age of the patient and the delay between injury and grafting. In addition, we found that nerve grafting without tension produces superior results over simple neurorrhaphy under tension and permits better axonal growth and nerve recovery. © 1994 Wiley-Liss, Inc.