Neuroscience
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This paper examines the topography of neuronal degeneration in the central nervous system of the dystonia musculorum (dt) mutant mouse, revealed by selective silver impregnation, specific histochemical staining and electron microscopy. Neuronal lesions have been observed exclusively in the spinal cord, the medulla and the anterior lobe of the vermis. In the spinal cord, axonal degeneration was maximal among large and medium-sized primary sensory fibers, whereas thin caliber primary afferents were unaffected, with the exception of those containing acid phosphatase activity. ⋯ This study also suggests a simple pathophysiological mechanism for the onset and the progression of the degeneration: dystonic gene action would affect perinatally specific classes of sensory receptors, producing the degeneration of the nerve terminals and, progressively, the cell death of the sensory ganglion cells at their origin. This retrograde death, which results in the massive and early deafferentation of spinocerebellar neurons, would provoke, trans-neuronally, the impairment of these second order sensory neurons and the progressive degeneration of the spinocerebellar system. The close resemblance of the neuropathology of the mutant mouse to Friedreich's ataxia (the commonest form of human degenerative ataxic disorders) allows one to suppose that the dystonic mouse may be an optimal animal model for studying the genetic basis and the pathophysiological mechanisms of this form of human ataxia.
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Specific antibodies raised in rabbits against 3-hydroxyanthranilic acid oxygenase (EC 1.13.11.6) and quinolinic acid phosphoribosyltransferase (EC 1.13.11.6) and quinolinic acid phosphoribosyltransferase (EC 2.4.2.19) were used in immunohistochemical studies to map the cellular localization of the quinolinic acid metabolizing enzymes in the adult male rat brain. 3-Hydroxyanthranilic acid oxygenase immunoreactivity was found to be present in glial cells of presumed astroglial identity, as judged by co-localization with glial fibrillary acidic protein. 3-Hydroxyanthranilic acid oxygenase-immunoreactive glial cells were present in all brain regions and within major fiber tracts. The density of 3-hydroxyanthranilic acid oxygenase-immunoreactive glial cells as well as the intensity of staining of these cells differed among brain regions. In general, telencephalic acid diencephalic areas harbored a larger number of 3-hydroxyanthranilic acid oxygenase-positive cells than did mesencephalic regions. ⋯ In addition to staining of glial cells, neuronal cell bodies containing 3-hydroxyanthranilic acid oxygenase immunoreactivity were detected in the main and in the accessory olfactory bulb, as well as in the ventromedial nucleus of the hypothalamus. Quinolinic acid phosphoribosyltransferase immunoreactivity was observed within glial cells and in association with neuronal cell bodies. Some, but not all, quinolinic acid phosphoribosyltransferase positive glial cells contained glial fibrillary acidic protein (Köhl
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Trimethyltin is a neurotoxicant which produces a distinct pattern of neuronal cell death following peripheral administration of a single dose (8 mg/kg, i.p.) in rats. The cupric-silver degeneration stain was used to produce an atlas documenting the distribution and time course of trimethyltin-induced neuronal damage in adult, male Long-Evans rats. Animals were examined at survival times of 1, 2, 3, 4, 5, 7, 10 and 18 days after intoxication. ⋯ Protein-O-carboxyl methyltransferase immunoreactivity was altered in neuronal populations damaged by trimethyltin, but did not appear to be either as sensitive or selective an assay of neuronal damage as the silver stain, especially at short survival times. Glial fibrillary acidic proteins were dramatically elevated 21 days after trimethyltin intoxication, particularly in areas of extensive damage. These studies revealed advantages and problems encountered in the use of each technique in assessing neurotoxic effects, forming a basis for discussion of the relative merits of using a battery of specific molecular probes for neurotoxicity evaluations.
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The rate of overflow and disappearance of dopamine from the extracellular fluid of the rat striatum has been measured during neuronal stimulation. Overflow of dopamine was induced by electrical stimulation of the medial forebrain bundle with biphasic pulse trains. The instantaneous concentration of dopamine was measured with a Nafion-coated, carbon fiber microelectrode implanted in the brain. ⋯ The increase in stimulated overflow observed after L-DOPA (250 mg/kg) could be modelled by a 1.6-fold increase in the amount of dopamine release with no alteration of the uptake parameters. The increase in modelled by an increase in Km. In addition, the fit of the modelled data to the experimental data was improved when diffusion from the release and uptake sites was considered.
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The localization of glycine receptors was immunocytochemically examined in the rat brain using a monoclonal antibody against the affinity-purified glycine receptor. Glycine receptors were concentrated in the lower brainstem, whereas no immunoreactivity was observed in the diencephalon and forebrain except in a few diencephalic nuclei. The highest density of receptors was found in the cranial motor nuclei, reticular formation, parabrachial area, dorsal and ventral cochlear nuclei, and dorsal and ventral tegmental nuclei. ⋯ In the cerebellar cortex, the immunoreactivity was exclusively seen along the dendrites of the Purkinje cells. On the other hand, glycine receptors were detected on the cellular membrane of the soma of the cochlear nuclei, trigeminal motor nucleus, parabrachial area, lateral reticular nucleus, dorsal nucleus of the lateral lemniscus, cerebellar nuclei, trigeminal spinal nucleus, anterior horn and reticular formation. In other regions, the receptors were evenly distributed throughout the neuropil.