Nicole Baumann

Absence of the major dense line in myelin of the mutant mouse "shiverer".

The myelin of the central nervous system (CNS) of the mutant mouse Shiverer is characterized by the absence of the major dense line (MDL). The intraperiod line, as seen in conventional electron micrographs and in freeze-fractured replicas, appears normal. Peripheral myelin, as seen in ventral and dorsal roots of spinal cord, is unaffected by the mutation. During the period of active myelination, the cytoplasm of most oligodendrocytes (ODs) is packed with electron-lucent vacuoles in continuity with the Golgi apparatus and with bundles of microtubules. It is concluded that a metabolic pathway possibly involving the Golgi apparatus, and contributing to the formation of the MDL is selectively affected in this mutant.

Immunochemical studies of myelin basic protein in shiverer mouse devoid of major dense line of myelin

The myelin-deficient mutant Shiverer (Shi/Shi) lacks basic protein (MBP) in the myelin of its central nervous system (CNS). Less than 3% of the normal content in MBP is present in a brain extract of Shi/Shi as determined by radioimmunoassay. Indirect immunofluorescence is negative when using specific anti-MBP serum. The importance of Shi/Shi (as compared to other hypomelinating mutants) stems from the specificity of this genetic lesion, i.e. the lack of basic protein.

Transplantation of CNS Fragments into the Brain of Shiverer Mutant Mice: Extensive Myelination by Implanted Oligodendrocytes

Solid fragments of olfactory bulb from new-born normal (B6CBA and C57BL6) mice were implanted into new-born shiverer (shi/shi) brains. The shiverer mouse being characterized by the absence of myelin basic protein (MBP), myelination due to implanted oligodendrocytes can be detected in the shiverer brain using an antiserum anti-MBP. Observation of sagittal sections of the host brains revealed very extensive areas of normal myelination from the level of the graft (rostral thalamus) up to the caudal brain (diencephalon, cerebellum, pons). Thus, oligodendrocytes contained in the implant migrate out of the graft over long distances in the host brain, before they differentiate and synthesize myelin. These results raise the question of the behaviour of oligodendrocytes in normal development.

Multifocal motor neuropathy with conduction block: a study of 24 patients.

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.

Peripheral neuropathy associated with IgM monoclonal gammopathy: correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases.

Forty cases of polyneuropathy associated with IgM monoclonal gammopathy were retrospectively studied to investigate the relevance of clinical and electrophysiological features to M‐protein antibody activity. There were 26 men and 14 women; mean age was 65 ± 11.7 years at the time of the study. Thirty‐nine patients had a symmetrical polyneuropathy, of whom 13 had a predominantly sensory and 17 a purely sensory neuropathy (i.e., 30 sensory neuropathies). The remaining patient had a multifocal mononeuropathy. Electrophysiological studies allowed the polyneuropathies to be classified as demyelinating in 33 cases (82.5%) and axonal in 6 cases. Antibody studies disclosed anti‐MAG antibodies in 65% and anti‐SGPG antibodies in 82.5% of patients. Anti‐MAG antibodies were associated with only demyelinating polyneuropathies. Anti‐SGPG antibodies were found in 91% of demyelinating polyneuropathies and 50% of axonopathies. In addition, anti‐MAG/SGPG antibody activity was significantly correlated with the subgroup of sensory neuropathies (P < 0.01). Last, antisulfatide antibodies were found at significant titers in 18 cases, and their presence was significantly correlated with anti‐MAG/SGPG antibody activity, but not with some clinical/electrophysiological features.

Determination of glial fibrillary acidic protein (GFAP) in human brain tumors.

Brain tumors have been tested for their glial fibrillary acidic protein (GFAP) content by means of the rocket electrophoresis technique. Meningiomas and neurinomas were low in GFAP. Metastases had a low level of GFAP except when contaminated with surrounding tissue. Non-nervous tumors such as myeloma, myeloplaxoma and adenocarcinoma gave negative results. More detailed correlations with histological observations have been looked for in glial tumors. Low levels of GFAP were always associated with signs of malignancy such as mitoses and giant or atypical cells, whereas high levels of GFAP were correlated with the presence of well-preserved astrocytes.

Survival and differentiation of oligodendrocytes from neural tissue transplanted into new-born mouse brain ☆

Fragments of new-born mouse central nervous system have been transplanted into new-born mice host brains, under conditions in which the myelin synthesized by the oligodendrocytes included in the graft, could be distinguished from the host myelin. The work demonstrates that transplanted oligodendrocytes survive in the host brain, migrate out of the graft and synthesize myelin. No sign of rejection was observed during the time of the experiment.

Immunohistochemical localization of galactosyl and sulfogalactosyl ceramide in the brain of the 30-day-old mouse

We have used purified antibodies against galactosylceramide (galCb) and sulfogalactosylceramide (sulf) to study the topographical distribution of these two lipid haptens in the brain of the 30-day-old mouse. This study has been conducted, using the indirect immunofluorescence method, on cerebellum, brain stem and hemispherical tissue sections. Both haptens are present in the myelin sheaths and in the oligodendrocytes within the myelinated bundles. Cortical oligodendrocytes as well as some of the subependymal cells are also galCb-positive but sulf-negative. On the contrary, ciliated ependymal cells and subpial astrocytic processes (especially the Bergmann glia fibers in the cerebellum) are sulf-positive and galCb-negative. Astrocyte cell bodies and other astrocytic cell processes are devoid of both haptens. Lastly, some-sulf positive galCb-negative processes, as yet unidentified, were also found in the periaqueductal gray matter and in the nucleus interpeduncularis.

Remyelination by transplanted oligodendrocytes of a demyelinated lesion in the spinal cord of the adult shiverer mouse

Fragments of normal newborn mouse central nervous system (CNS) were transplanted into the spinal cord of adult shiverer mice at distance of 1, 2 or 3 intervertebral spaces from a lysolecithin-induced demyelinating lesion. Remyelination by grafted oligodendrocytes was observed by electron microscopy (EM). This result showed the capability of grafted oligodendrocytes or precursor cells to migrate to a demyelinated lesion and to remyelinate naked axons in an adult host, even in presence of host spontaneous remyelination.

Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines

Phenothiazines and tricyclic antidepressants, when added to culture medium, gave rise in several types of cells (C6 rat glioma cells and human fibroblasts), to a decrease in lysosomal sphingomyelinase activity. The effect of chlorpromazine and desipramine was dose dependent, and was observed after 3 hours of incubation with the drugs at concentrations ranging between 1 and 10 microM. In C6 glioma cell cultures, the decrease in sphingomyelinase activity was related to the clinical effectiveness of phenothiazines, tricyclic antidepressants and derivatives. Incorporation of (choline-14C) sphingomyelin showed that the metabolic pathway implying the synthesis of phosphatidylcholine from the hydrolysis of sphingomyelin and/or transfer of phosphorylcholine to phosphatidylcholine was also partially reduced.