9 research outputs found
Successful management of dexmedetomidine for postoperative intensive care sedation in a patient with anti-NMDA receptor encephalitis: a case report and animal experiment
Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells
The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis
Antibiotic Treatment Attenuates Behavioral and Neurochemical Changes Induced by Exposure of Rats to Group A Streptococcal Antigen
The B cell immunobiology that underlies CNS autoantibody-mediated diseases
A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy, patients with these neuroglial surface autoantibody (NSAb)-mediated diseases often experience clinical relapse, high rates of long-term morbidity and adverse effects from the available medications. Fundamentally, the autoantigen-specific B cell lineage leads to production of the pathogenic autoantibodies. These autoantigen-specific B cells have been consistently identified in the circulation of patients with NSAb-mediated diseases, accompanied by high serum levels of autoantigen-specific antibodies. Early evidence suggests that these cells evade well-characterized B cell tolerance checkpoints. Nearer to the site of pathology, cerebrospinal fluid from patients with NSAb-mediated diseases contains high levels of autoantigen-specific B cells that are likely to account for the intrathecal synthesis of these autoantibodies. The characteristics of their immunoglobulin genes offer insights into the underlying immunobiology. In this Review, we summarize the emerging knowledge of B cells across the NSAb-mediated diseases. We review the evidence for the relative contributions of germinal centres and long-lived plasma cells as sources of autoantibodies, discuss data that indicate migration of B cells into the CNS and summarize insights into the underlying B cell pathogenesis that are provided by therapeutic effects
The nano-architecture of the axonal cytoskeleton
International audienceThe cytoskeleton is a cellular shapeshifter. Like these creatures of mythology and speculative fiction, the cytoskeleton can alter its physical form and shape to accommodate the immediate needs of the cell. Indeed, many a rapt student has watched the cytoskeleton of a dividing cell seemingly miraculously transform into an organized mitotic spindle and then dissolve into an indiscrete mass, right before their eyes. The extreme polarization of neurons (that is, their fundamental asymmetry, arising due to the presence of elongated processes), along with their lifelong plasticity, creates unique demands on the cytoskeleton. A remarkable example is the axon, which can grow to enormous lengths and must generate and maintain its form and function throughout life — a burden that rests largely on the cytoskeleton. The axonal cytoskeleton has three major constituents: microtubules, neurofilaments and actin (BOX 1). Each is unique, associating with its own set of binding proteins and performing specialized roles within the axon. Most of these cytoskeletal proteins are synthesized in the neu ronal soma and are transported along the axon. Such transport is a constitutive phenomenon that occurs throughout the life of the neuron. Thus, the axonal cytoskeleton is best understood by considering both its anatomical organization and its dynamics (including axonal transport). Given the complex morphology and physiology of neurons, the field of neurobiology has traditionally been at the forefront of adopting new optical techno logies as they arise. Advances in microscopy now allow us to observe cells with unprecedented spatial resolu tion and to follow dynamic processes with exquisite temporal detail 1. For example, superÂresolution strat egies that circumvent the diffraction limit of optical microscopy appeared more than ten years ago (BOX 2) and have been used to reveal aspects of neuronal organ ization down to the scale of macromolecular com plexes 2. These techniques have provided key insights into the organization and function of the axonal cytoskeleton — and in particular the organization of actin and microtubules — revealing how it builds the axon and maintains its intricate architecture. Focusing on the cytoskeleton within the axon initial segment (AIS) and the more distal axon shaft, in this Review, we highlight these recent discoveries and place them in the context of earlier findings, giving the reader a tentative vision of the future. Overview of the axonal cytoskeleton The history of cytoskeletal research is essentially the pursuit of tools and techniques that allowed an ever closer view of this elaborate structure, a quest that continues to this day. Early studies by 17thÂcentury microscopy pioneers highlighted a network of 'neu rofibrils' , which we now know were most likely neuro filaments 3. With the advent of electron microscopy, two types of fibrils were seen in axons: filaments measuring approximately 10 nm in diameter, corresponding to neurofilaments, and others measuring approximately 20–30 nm in diameter, corresponding to structures that eventually came to be known as microtubules 4,5. Abstract | The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton