Chemically induced degeneration of indoleamine-containing nerve terminals in rat brain.
Explore the source record for details and available documents.
SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of the catecholamine neurotoxic compound, 6-hydroxydopamine (6-OHDA) have been investigated on central noradrenaline (NA) neurons after neonatal administration. In agreement with previous studies this treatment (1-3 X 100 mg/kg) led to a pronounced reduction of the in vitro uptake of [3H]NA and the endogenous NA in the cerebral cortex, while these parameters were markedly augmented in the pons and medulla oblongata, regions containing the NA perikarya. The 6-OHDA induced changes in the cerebral cortex and the pons-medulla could be completely prevented by the 'membrane pump' blocker desipramine, indicating that the effects are associated with a specific neurotoxic action of 6-OHDA on the NA neurons. Consistently, 6-OHDA acutely (within 2 h) produced a marked reduction of the [3H]NA uptake in both the cerebral cortex and pons-medulla. In the cerebral cortex the nadir (approximately 75% reduction) was reached within 6 h and remained so, while in the pons-medulla the [3H]NA uptake rapidly recovered, being maximally elevated after 14 days (50-80% increase) and remained so for at least 6 months. The [3H]NA uptake in the pons-medulla from 6-OHDA treated rats had the same kinetic and pharmacological properties as that of control. Thus the observed differences in [3H]NA uptake are most likely quantitatively related to actual changes in the number of NA nerve terminals. Treatment with lower 6-OHDA doses (10 or 50 mg/kg) resulted in less pronounced reduction of [3H]NA uptake initially, and there was a gradual recovery of tuptake with time in the cerebral cortex, which was more pronounced after the lower dose. These results are indications of regenerative growth, which may be possible when a critical part of the axon is spared from the neurotoxic effect of 6-OHDA. Administration of 6-OHDA on various days after birth disclosed that both the reduction of [3H]NA uptake in the cerebral cortex and the increase of [3H]NA uptake in the pons-medulla did not appear as permanent phenomena when 6-OHDA was given later than on the seventh postnatal day. This is most likely associated with the postnatal development of the blood-brain barrier. It may be concluded that the neonatal 6-OHDA treatment causes a marked NA denervation in the forebrain, e.g. the cerebral cortex, and an increased outgrowth of NA nerve terminals in the pons-medulla, which is preceded by a partial damage. This partial NA denervation is then followed by a regeneration (regenerative and/or collateral sprouting) and a stimulated outgrowth of NA nerve terminals.
Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 1.14.16.2) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 1.14.17.1) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons.
Explore the source record for details and available documents.
After the destruction of the noradrenergic ascending pathways, the localization of frontal cortical fields receiving fibers from the dopaminergic mesocortical system has been studied in rats, using a glyoxylic-paraformaldehyde method. The dopaminergic innervation was distributed in two main areas. The area of highest density was a medial field which spread in the medial cortex anterior and dorsal to the genu of the corpus callosum. It did not reach the shoulder region except in the foremost part of the frontal lobe where dopaminergic fibers were scattered in the whole cortex, including the molecular layer. A deep sulcal field was situated between the dorsal bank of the rhinal sulcus and the lateral cortex above it. In addition, a moderately dense band of dopaminergic fibers was observed between the corpus callosum and the anterior commissura, beside the accumbens nucleus. Similar data were obtained with dopamine uptake experiments on reserpine-treated but otherwise normal animals. The frontal areas receiving dopaminergic innervation coincide strikingly with the 'prefrontal cortex' as defined by neuroanatomical studies, which is assumed to be more or less equivalent to the prefrontal cortex of primates and derives direct projections from the amygdala. The functional implications of these findings are discussed.
Uptake of 5-hydroxytryptamine (5-HT) by adult and fetal rabbit's ileum was studied. The adult myenteric plexus accumulated tritium when incubated with tritiated 5-HT. However, in addition to labeled 5-HT, tritiated 5-hydroxyindole acetic acid and, when monoamine oxidase (MAO) was inhibited, 5-HT-o-glucuronide were found in the tissue. Two uptake processes differing in affinity could be defined. Only the high affinity process was saturable. Fetal ileum took up tritiated 5-HT but glucuronidation did not occur when MAO was inhibited. The uptake of tritiated 5-HT by the fetal ileum was due to a single, saturable, temperature sensitive (Q10 at 27-37 degress C = 2.4) process inhibited by ouabain. It was identical to the high affinity uptake found in adult tissue. This specific high affinity uptake could be found as early as the 16th day of gestation, 5-8 days before uptake of norepinephrine (NE) begins. Light and electron microscope radioautography revealed that the uptake of 5-HT was primarily into axons and a characteristic structure called the expanded process, both in the myenteric plexus. Both contained dense-cored vesicles. Axons were not labeled by tritiated NE until after 24 days and the expanded process was never labeled by tritiated NE. This study shows that uptake of 5-HT is a property of distinct system of axons in the mammalian myenteric plexus which develops prior to adrenergic axons during ontogeny.
Explore the source record for details and available documents.
Extensive plexuses of serotonin axons form a supra- and subependymal system in the walls of the ventricles, in the arachnoid sheath around major cerebral blood vessels, and in the pia over the spinal cord. These have been demonstrated by autoradiography after continuous intraventricular perfusions of exogenous [3H]5-HT in rats and monkeys. The axons accumulate 5,6-DHT rendering them electron opaque, but have no uptake systems for [3H]NE. After treatment with MAO inhibitors and [3H]5-HT, the axonal boutons contain large (70nm) variably dense synaptic vesicles, and small (35 nm) vesicles each equipped with a dense dot. The latter vesicles are not seen in untreated controls. Electrical stimulation in the raphe nuclei causes significant increases in axonal [3H]5-HT uptake indicating that the fibers originate in the raphe. Quantitatively, the supraependymal plexus is variable, profuse over the dorsal and ventral aqueductal surfaces, sparse over the lateral aspects. Individual raphe neurons have their specific uptake affinities for [3H]5-HT that are independent of tracer concentration or diffusion gradient. It is suggested that raphe neurons with low 5-HT uptake may utilize other neurotransmitters. Two new functional roles are proposed: (1) the serotonin ventricular and pial axons are probably important modifiers of local cerebrospinal fluid (CSF) composition so that regional CSF variations in 5-HT and its metabolites are highly probable; (2) the subarachnoid plexus around major cerebral vessels may contribute to local vasomotor action, thus affecting the cerebral blood flow. The possible significance of these serotonin systems for an understanding of certain neurological entities such as migraine and hemodynamic regulation in cerebral vascular disease is indicated.
Slices obtained from the deeper layers of the rat dorsal frontal, parietal and occipital brain cortex were incubated in vitro with 6.25 X 10-7 M [3H]dopamine (DA), and subsequently superfused and electrically stimulated, while held on quick transfer electrodes, and changes in the efflux of 3H and of the individual amines measured. The separation of the amines, with quantitative recoveries, was performed by chromatography on cation-exchange resins eluted sequentially with water, 1 N HCL AND 6 M urea i 1 N HCl. When no drugs were used, the prestimulation efflux was entirely formed by deaminated metabolites, while following stimulation there was an increase in the efflux of deaminated metabolites, and considerable amounts of [3H]-noradrenaline (NA) now appeared. No DA was present in the pre- or poststimulation medium. Similar results were obtained in all the regions studied. When the slices were incubated with 10-5 M desmethylimipramine (DMI), 10-4 Mnialamide and 10-4 M tropolone, before and during incubation with [3H]DA, it was observed that, prior to stimulation, the efflux was composed of deaminated metabolites, DA and 3-methoxytyramine (MTA), and following the electrical stimulus there was an increased release of DA, NA and deaminated compounds (in order of decreasing release), while no change in that of MTA was evident. The stimulus-induced release of DA was greatest from frontal slices, intermediate from parietal, and lowest from occipital ones. DMI-resistant uptake of [3H]DA also diminished when passing from frontal to occipital. These findings are interpreted as due to the presence of dopaminergic axon terminals in all the regions studied, but with a density that diminishes in a rostrocaudal direction.
Explore the source record for details and available documents.
Explore the source record for details and available documents.