A semiquantitative, electron microscopic immunocytochemical procedure based on the use of colloidal gold particles as markers was employed to analyze the subcellular distribution of glutamate and glutamine, a major glutamate precursor, in a subpopulation of spinocerebellar mossy fiber terminals. These terminals were identified by anterograde transport of a horseradish peroxidase-wheat germ agglutinin conjugate, injected in the thoracic spinal cord. Gold particles signalling glutamate-like immunoreactivity were enriched over clusters of synaptic vesicles relative to organelle-free cytoplasmic matrix, and there was a strong positive correlation between gold particle and synaptic vesicle densities (correlation coefficient 0.94). Gold particles indicating glutamine-like immunoreactivity showed a much weaker correlation with vesicle density (correlation coefficient 0.36) and were about equally concentrated over cytoplasmic matrix as over clusters of synaptic vesicles. Compared with the mossy fibers, the putative GABAergic Golgi cell terminals exhibited a lower level of glutamate-like immunoreactivity, which was very weakly correlated with the vesicle density (correlation coefficient 0.27). The level of glutamine-like immunoreactivity in the Golgi cell terminals was similar to that in mossy fibers, but much lower than that in glial cells. The anterogradely labelled mossy fiber terminals were not enriched in immunoreactivities for aspartate or GABA. These results suggest that the level and subcellular distribution of glutamate in presumed glutamatergic terminals differs from that in terminals in which glutamate only serves metabolic or precursor roles, and that these differences can be exploited in immunocytochemical studies aimed at identifying glutamate-using neurons. In contrast, glutamine immunocytochemistry does not seem to be generally useful in this regard.
Many mossy fiber afferent projections to the rat cerebellar cortex terminate in parasagittal bands. In particular, the anterior lobe vermis of the cerebellum contains alternating bands of mossy fibers from the spinal cord and external cuneate nuclei. The cerebellar cortical efferents, the Purkinje cells, are also organized in parasagittal bands. These can be revealed by immunochemical staining for the antigen zebrin II, which is selectively expressed by bands of Purkinje cells. In some cases, the boundaries between mossy fiber terminal fields align with identified transitions between zebrin+/- sets of Purkinje cells, whereas others are located within apparently homogeneous Purkinje cell compartments. Two theories can explain the terminal-field topography: In one view, mossy fiber terminals segregate during development, because growth cones from different sources compete for common territory. Alternatively, mossy fiber growth cones directly recognize chemically distinct target territories, and activity-dependent mechanisms play only minor roles. To explore these issues, two sets of experiments were performed. First, the terminal-field map of the neonatal spinocerebellar projection was compared to the Purkinje cell compartmentation as revealed by anticalbindin immunocytochemistry. Second, subsets of spinocerebellar mossy fiber afferents were ablated early in postnatal development, and the consequences for the neighboring cuneocerebellar terminal fields were mapped in the adult with reference to the zebrin II+/- compartments. These experiments revealed no evidence that competitive interactions constrain the mossy fiber terminal-field distribution but, rather, suggest that the organization of the mossy fiber projections follows the compartmentation of the Purkinje cells.
Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing-remitting multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.
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