Thymus grafts induce B cell development in nude, X-linked immune deficient mice

Mice simultaneously expressing the mutations nude and X-linked immune deficiency (xid) were previously shown to have pro-B cells and/or early pre-B cells while lacking C mu+ and surface Ig+ cells. We now report that thymus grafts restore both T cells and B cells in nude-xid mice. By the use of Thy-1 and Igh allogeneic donors it was shown that both the T and B cells were host derived. The B cells had a functional phenotype typical of xid mice. It is concluded that the maturation of xid B cells past the pro-B or early pre-B stage is T cell dependent.     

Illusory ownership of a virtual child body causes overestimation of object sizes and implicit attitude changes

An illusory sensation of ownership over a surrogate limb or whole body can be induced through specific forms of multisensory stimulation, such as synchronous visuotactile tapping on the hidden real and visible rubber hand in the rubber hand illusion. Such methods have been used to induce ownership over a manikin and a virtual body that substitute the real body, as seen from first-person perspective, through a head-mounted display. However, the perceptual and behavioral consequences of such transformed body ownership have hardly been explored. In Exp. 1, immersive virtual reality was used to embody 30 adults as a 4-y-old child (condition C), and as an adult body scaled to the same height as the child (condition A), experienced from the first-person perspective, and with virtual and real body movements synchronized. The result was a strong body-ownership illusion equally for C and A. Moreover there was an overestimation of the sizes of objects compared with a nonembodied baseline, which was significantly greater for C compared with A. An implicit association test showed that C resulted in significantly faster reaction times for the classification of self with child-like compared with adult-like attributes. Exp. 2 with an additional 16 participants extinguished the ownership illusion by using visuomotor asynchrony, with all else equal. The size-estimation and implicit association test differences between C and A were also extinguished. We conclude that there are perceptual and probably behavioral correlates of body-ownership illusions that occur as a function of the type of body in which embodiment occurs.     

Localization of molluscan R15α2 peptide immunoreactivity in the mammalian brain

The R15 neuropeptides have been identified in the marine molluscAplysia californica. They compose a new family of neuropeptides acting on the cardiovascular, digestive, respiratory, reproductive and nervous system. In this report we show that one of the members of the R15 neuropeptide family, the α2 peptide is conserved in lower mammals. We have identified R15α2 immunoreactive neurons in the neurosecretory cell groups of the hypothalamus and in the brainstem of the hedgehog (Erinaceus europaeus). The majority of labeled cells were localized to the anterior periventricular part of the paraventricular nucleus and the accessory neurosecretory cell groups in the lateral hypothalamus as well as to the dorsal part of the nucleus tractus solitarii. In the paraventricular nucleus, R15α2 immunoreactive neurons also exhibit immunoreactivity for oxytocin, cortocotropin releasing factor, vasoactive intestinal polypeptide and for the FMRFamide-related peptide which we found to be conserved in the hedgehog brain as well. No complete colocalization of R15α2 with any of the neuroactive substances tested, is observed. The highest degree of coexistence occurs with FMRFamide-related peptide, followed by vasoactive intestinal polypeptide, oxytocin and corticotropin releasing factor.     

From the Cover: Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals

Gray matter pathology is increasingly recognized as an important feature of multiple sclerosis (MS), but the nature of the immune response that targets the gray matter is poorly understood. Starting with a proteomics approach, we identified contactin-2/transiently expressed axonal glycoprotein 1 (TAG-1) as a candidate autoantigen recognized by both autoantibodies and T helper (Th) 1/Th17 T cells in MS patients. Contactin-2 and its rat homologue, TAG-1, are expressed by various neuronal populations and sequestered in the juxtaparanodal domain of myelinated axons both at the axonal and myelin sides. The pathogenic significance of these autoimmune responses was then explored in experimental autoimmune encephalitis models in the rat. Adoptive transfer of TAG-1–specific T cells induced encephalitis characterized by a preferential inflammation of gray matter of the spinal cord and cortex. Cotransfer of TAG-1–specific T cells with a myelin oligodendrocyte glycoprotein-specific mAb generated focal perivascular demyelinating lesions in the cortex and extensive demyelination in spinal cord gray and white matter. This study identifies contactin-2 as an autoantigen targeted by T cells and autoantibodies in MS. Our findings suggest that a contactin-2–specific T-cell response contributes to the development of gray matter pathology.     

Localization of CRMP5 mRNA by in situ hybridisation during development of the mouse forebrain

The expression of the collapse response mediator protein CRMP5 in the prenatal mouse is largely unknown. Evidence suggests that CRMP family members play important roles in neurite outgrowth, and CRMP5 is known to modulate outgrowth of processes in oligodendrocytes through signalling via neuropilin-1 and SemaA. Furthermore, CRMP family members function in axon regeneration after injury and are implicated in the early stages of Alzheimer's disease. Despite these findings relatively little is known about the specific roles these proteins play. The aim of the present study was to evaluate CRMP5 expression in the developing mouse forebrain using in situ hybridisation. Serial coronal sections of brain from E12.5 to E18.5 were analysed. We found highly specific patterns of expression which were restricted to the post-mitotic layers of both the ganglionic eminence and neocortex, and an additional domain of strong expression in the pyramidal layers of the hippocampus in all prenatal ages. Our results are therefore consistent with a role for CRMP5 in process extension. Interestingly, our results also revealed a temporal switch in high-expression levels from the ganglionic eminence to the cortex at a critical time during tangential cell migration. However, the pattern of expression appeared more representative of a general permissiveness for neurite outgrowth rather than one which is restricted to a particular cell subset or cell class. Additionally, expression was also found during periods predominated by neurogenesis and not neurite extension. We conclude that expression of CRMP5 is consistent with a dynamic implicit role in forebrain development.     

Regional distribution and cell type-specific expression of the mouse F3 axonal glycoprotein: a developmental study.

The expression of the mouse axonal adhesive glycoprotein F3 and of its mRNA was studied on sections of mouse cerebellar cortex, cerebral cortex, hippocampus, and olfactory bulb from postnatal days 0 (P0) to 30 (P30). In cerebellar cortex, a differential expression of F3 in granule versus Purkinje neurons was observed. F3 was highly expressed during migration of and initial axonal growth from cerebellar granule cells. The molecule was then downregulated on cell bodies and remained expressed, although at low levels, on their axonal extensions. On Purkinje cells, F3 was strongly expressed on cell bodies and processes at the beginning of the second postnatal week; by P16 it was restricted to neurites of Purkinje cells subpopulations. In the cerebral cortex, the molecule was highly expressed on migrating neurons at P0; by P16, it was found essentially within the neuropil with a diffuse pattern. In the hippocampal formation, where F3 was expressed on both pyramidal and granule neurons, a clear shift from the cell bodies to neurite extensions was observed on P3. In the olfactory pathway, F3 was expressed mainly on olfactory nerve fibers, mitral cells, and the synaptic glomeruli from P0 to P3, with a sharp decline from P11 to P16. As a whole, the data show that F3 protein expression is regulated at the regional, cellular, and subcellular levels and suggest that, in different regions, it can be proposed as a reliable neuronal differentiation marker.     

Effects of Task Organization on the Independent Play of Students with Autism Spectrum Disorders

The purpose of the study was to examine the impact of task organization, a component of Structured Teaching developed by Division TEACCH, on the independent play of children with autism spectrum disorders (ASD). On-task behavior, task accuracy, task performance and teacher prompting were measured across independent play sessions in the classroom. An ABAB design was implemented to evaluate the effects of task organization on the independent play skills of two young children with ASD. Results regarding on-task behavior, task accuracy and independence were variable and are discussed. The implications of findings on the use of task organization for increasing independence in children with ASD are discussed.     

The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone‐induced death,through the NGF receptor TrkA

BNN27, a member of a chemical library of C17‐spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75^NTR), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA‐dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro. The effect of BNN27 in the cuprizone mouse model of demyelination in vivo has also been investigated. In this model, that does not directly involve the adaptive immune system, BNN27 can protect from demyelination without affecting the remyelinating process. BNN27 preserves mature oligodendrocyte during demyelination, while reducing microgliosis and astrogliosis. Our findings suggest that BNN27 may serve as a lead molecule to develop neurotrophin‐like blood–brain barrier (BBB)‐permeable protective agents of oligodendrocyte populations and myelin, with potential applications in the treatment of demyelinating disorders.     

Sympathetic and sensory neural elements in the tendon of the long head of the biceps

BACKGROUND: Although the tendon of the long head of the biceps is a well-known source of shoulder pain, the pathophysiological basis of this pain has yet to be explained. The aim of this study was to detect and characterize any nervous element of the tendon and to determine a possible explanation for pain originating from this structure. METHODS: The nature of the neuronal innervation of the tendon of the long head of the biceps was studied immunohistochemically, in four tendons from different human cadavers, with use of neurofilament antibody 2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase. RESULTS: A large neuronal network, asymmetrically distributed along the length of the tendon with a higher degree of innervation at the tendon origin, was identified by the neurofilament and neurofilament-like antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin gene-related peptide and substance P, suggesting the presence of thinly myelinated or unmyelinated sensory neurons. It was also positive for tyrosine hydroxylase, suggesting a post-ganglionic sympathetic origin. CONCLUSIONS AND CLINICAL RELEVANCE: These findings demonstrate that the tendon of the long head of the biceps is innervated by a network of sensory sympathetic fibers, which may play a role in the pathogenesis of shoulder pain.