Biomedical subjects

V Lev-Ram

Publications and source records attributed to V Lev-Ram.

25 records · Page 2Linked to original sources

PubMed1986

Ca2+- and K+-dependent communication between central nervous system myelinated axons and oligodendrocytes revealed by voltage-sensitive dyes.

The interactions between myelinated axons and surrounding glia cells, in rat optic nerve, were investigated by optical recording with voltage-sensitive dyes. Electrical stimulation of the nerve evoked an optical signal revealing two clearly distinct components: a fast propagating component, corresponding to the compound action potential, and a prominent slow component. Several lines of evidence suggest that part of the slow component originated from depolarization of the oligodendrocytes by potassium accumulation in the paranodal or internodal region. In addition, the experiments suggest that in this preparation axons also have voltage-dependent Ca2+ channels, and a Ca2+-dependent K+ conductance involved in the depolarization of oligodendrocytes. Thus, axons and oligodendrocytes communicate in an intimate, ionically-mediated fashion, and oligodendrocytes may play an important functional role beyond that of providing the myelin sheath.

Action Potentials↗

PubMed1984

Monoclonal antibodies associated with sodium channel block nerve impulse and stain nodes of Ranvier.

Monoclonal antibodies were generated against native eel electroplax sodium channels in their natural membrane. These antibodies block nerve conduction in rat central (optic) and peripheral (sciatic) nerve. The antibody binding to eel electroplax membrane fragments and to rat brain synaptosomes can be modulated by neurotoxins. Thus it implies that active sites of the sodium channels are immunogenic in their natural membrane. Unlike the antibodies described in the past, our antibodies recognize antigenic determinants which are associated with the physiological activity of the channel and have been conserved through evolution.

Animals↗

PubMed1984

Immunological expression of gangliosides in multiple sclerosis and in a demyelinating model disease in rabbits.

Accumulating evidence suggests that the process of demyelination in MS might involve an autoimmune response to one or more myelin components. A combination of myelin basic protein and myelin haptens was considered as possibly enhancing a cellular or humoral autoimmune reaction in MS. In line with this motion we have used an in-vitro E-rosette assay that correlates with in-vivo delayed hypersensitivity to demonstrate specific immunologic sensitivity of lymphocytes from MS patients to polysialogangliosides. A recent report that only lymphocytes from patients in relapse, but not in remission, are primed by gangliosides, underscores the relevance of the antigenic expression of gangliosides during the active pathological phase of the disease. The antigenic capacity of gangliosides to induce upon immunization a neurological disorder featured by demyelination in the CNS was demonstrated in rabbits. This and previous reports on the induction of peripheral demyelination in rabbits immunized with gangliosides will be further analyzed to gain insight on the possible role of these myelin lipid components as targets for an autoimmune mechanism in MS.

Adult↗

PubMed1982

Abnofmalities in brain myelin or rabbits with experimental autoimmune multiple sclerosis-like disease induced by immunization to gangliosides.

An experimental autoimmune multiple sclerosis-like disease (EAMSD) was induced in rabbits by immunizing them with bovine brain gangliosides. Forebrain myelin was isolated and fractionated on a discontinuous sucrose gradient into light myelin (LM, buoyant density less than or equal to 0.625 M), and heavy myelin (HM, buoyant density greater than 0.625 M). No abnormalities in either protein or lipid composition of EAMSD myelin fractions were observed. However, the EAMSD tissue yielded 31% less light and 39% more heavy myelin compared to the control brains. Thus, the HL/LM ratio was two-fold greater in experimental than in control myelin. This pathological pattern is similar to that which has been observed in myelin obtained from the brains of multiple sclerosis patients and from the optic nerves of rabbits with experimentally-induced demyelination.

Animals↗

PubMed1979

Immune response genes have a variable influence on the selection of antigenic foreign and self determinants of insulin.

We studied the proliferative response of mouse T lymphocytes to determinants on ungulate insulins. The immunopotency of defined determinants on the molecule was found to be regulated by three factors: the immune response genes of the immunized mouse, the mode of presentation of insulin on cells or in adjuvant, and the intramolecular cooperativity between different determinants on the insulin molecule. Autosensitization against self determinants was observed under specific conditions. These findings emphasize the variable expression of immune response genes.

Animals↗

PubMedDate not supplied

Immunospecific inhibition of nerve conduction by T lymphocytes reactive to basic protein of myelin.

Experimental autoimmune encephalomyelitis (EAE) induced by immunization to the basic protein of central nervous system myelin (BP) is a paralytic disease in which T lymphocytes attack the individual's own central nervous system. As the target is in white matter, EAE has been considered an experimental model of some aspects of human disease such as multiple sclerosis. To investigate whether autoimmune T lymphocytes could produce paralysis, we studied the effects on the electrophysiology of isolated nerves produced by T-lymphocyte lines reactive specifically to BP or other antigens. We now report that propagation of action potentials evoked by electrical stimulation was blocked by incubating optic nerves with specific anti-BP T cells. This blockade could be reversed for up to two hours by removing the anti-BP line cells from the optic nerve. The anti-BP line cells had no effect on conduction along allogeneic optic nerves or syngeneic peripheral nerves. This indicates that disruption of the function of myelin in neuroimmunological disease may result from an immunologically specific interaction between autoimmune T lymphocytes and myelin antigens.

Action Potentials↗

PubMedDate not supplied

Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase.

Extensive pharmacological evidence suggests that nitric oxide (NO) is a crucial transmitter for cerebellar long-term depression (LTD), a long-lasting decrease in efficacy of the synapses from parallel fibers onto Purkinje neurons, triggered by coincident presynaptic activity and postsynaptic depolarization. We now show that LTD cannot be induced in Purkinje neurons under whole-cell patch clamp in cerebellar slices from young adult mice genetically lacking neuronal nitric oxide synthase (nNOS). This genetic evidence confirms the essentiality of NO and nNOS for LTD in young adult rodents. Surprisingly, LTD in cells from nNOS knockout mice cannot be rescued by photolytic uncaging of NO and cGMP inside Purkinje neurons, although such stimuli circumvent acute pharmacological inhibition of nNOS and soluble guanylate cyclase in normal rodents. Also slices from knockout mice show no deficit in cGMP elevation in response to exogenous NO. Therefore, prolonged absence of nNOS allows atrophy of the signaling pathway downstream of cGMP.

Animals↗