Antibodies for neuroscience research (original) (raw)

Antibodies as molecular probes in neurobiology

Molecular Neurobiology, 1992

Immunocytochemical localization of 5-hydroxytryptamine (5-HT) in the nervous system and aggregate tissue cultures was performed employing an antibody to 6-OH-1,2,3,4-tetrahydro-β-carboline. A number of immunochemical and biochemical tests with the antigen and the antibody and some procedural changes in the methodology applied for immunolocalization revealed the anti-5-HT-like affinity of the antibody, if applied in paraformaldehyde-fixed tissues. Studies in the hypothalamus, striatum, brainstem, spinal cord, and pineal gland show the complexities of the serotoninergic system. Ultrastructural immunocytochemistry with the preembedding technique reveals that 5-HT synapses are of the asymmetric type. The presynaptic element contains clear, round, small vesicles, with some large dense-core vesicles. The contacts are made with the somata and primary, secondary dendrites or with spines of non-5-HT neurons. Presynaptic dendrites are found in the n. raphe dorsalis, contacting non-5-HT dendrites. Double immunocytochemical methods demonstrated contacts of 5-HT fibers on enkephalin containing neurons of the spinal trigeminal nucleus and on somatostatin containing neurons of the medullary reticular formation. In vitro studies of cultured mesencephalic neurons were performed with the method of aggregating cultures. Such development of a miniature organized nerve tissue was followed up to 35 d in culture. Organization of the neuropil and synaptogenesis was studied using standard electron microscopy. The differentiation of neurons and astrocytes was studied using antibodies to 5-HT and GFAP. Serotonin immunoreactivity could be observed in neuronal bodies and processes at light microscope level as early as the fourth day of culture. The length of neuronal projections increased to form extensive networks. The GFAP immunolabeling could be observed in astrocytes, forming a perinuclear ring, after 5 d of culture. Later, immunoreactivity spread to glial processes acquiring a differentiated fenotype.

Monoclonal Antibodies as Neurological Therapeutics

Pharmaceuticals

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies a...

A monoclonal antibody that binds to both astrocytes and myelin sheaths

Journal of Neuroimmunology, 1985

A monoclonal antibody designated III 5H8 was shown to bind both to astrocytes and to myelin sheaths as studied with immunocytochemical techniques on brain sections and cell cultures. Binding to astrocytes was confirmed by double immunofluorescent labelling of frozen sections and cell cultures with anti-GFAP, and appeared to be sensitive to formalin treatment. Binding to myelin sheaths was confirmed by comparing sections labelled with III 5H8 with sections labelled with antibodies against axons and myelin basic protein as well as by staining of sections of hypomyelinated spinal cord with III 5H8. On immunoblots of separated white matter III 5H8 revealed two bands, while on immunoblots of purified myelin only one band was seen. The findings are discussed with respect to the function of astrocytes in white matter and shared antigenic determinants between astrocytes and oligodendrocytes.

Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases

JAMA Neurology, 2015

Modulating the immune system does not reverse long-term disability in neurologic disorders. Better neuroregenerative and neuroprotective treatment strategies are needed for neuroinflammatory and neurodegenerative diseases. To review the role of monoclonal, naturally occurring antibodies (NAbs) as novel therapeutic molecules for treatment of neurologic disorders. Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized clinical trials, and basic science reports, were identified in a PubMed search for articles about NAbs and neurologic disorders that were published from January 1, 1964, through June 30, 2015. We concentrated our review on multiple sclerosis, Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. Many insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system. Central nervous system injury often results in a pervasive inhibitory microenvironment that hinders regeneration. A common targeted drug development strategy is to identify molecules with high potency in animal models. Many approaches often fail in the clinical setting owing to a lack of efficacy in human diseases (eg, less than the response demonstrated in animal models) or a high incidence of toxic effects. An alternative approach is to identify NAbs in humans because these therapeutic molecules have potential physiologic function without toxic effects. NAbs of the IgG, IgA, or IgM isotype contain germline or close to germline sequences and are reactive to self-components, altered self-components, or foreign antigens. Our investigative group developed recombinant, autoreactive, natural human IgM antibodies directed against oligodendrocytes or neurons with therapeutic potential for central nervous system repair. One such molecule, recombinant HIgM22, directed against myelin and oligodendrocytes completed a successful phase 1 clinical trial without toxic effects with the goal of promoting remyelination in multiple sclerosis. Animal studies demonstrate that certain monoclonal NAbs are beneficial as therapeutic agents for neurologic diseases. This class of antibodies represents a unique source from which to develop a new class of disease-modifying therapies.