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• W2023248876 abstract "The effect of 6-hydroxydopamine (6-OH-DA) on the central nervous system was studied with light, fluorescence and electron microscopy. The drug was administered intracerebrally, intraventricularly or in vitro. Special attention was paid to the effect on the nigro-neostriatal dopamine (DA) system after intracerebral injections over the cell bodies in the substantia nigra or on the terminals in the striatum. Furthermore, the extent of unspecific damage caused by this drug was evaluated. Twenty-four to 72 h after the injection of 6-OH-DA into the substantia nigra marked effects on the nigral cell bodies were seen. In the fluorescence microscope the normally green fluorescent cell bodies showed a clear yellow colour paralleled by a decrease in size. In the glutaraldehyde-OsO 4 fixed material for light and electron microscopy the cell bodies showed marked swellings and disintegration. However, only a certain population of the cell bodies of the zona compacta were affected, whereas other cell bodies intermingled showed no obvious changes in their fine structural features. The neurones unaffected by 6-OH-DA had characteristic ultrastructural features such as an indented nucleus and light cytoplasm with a sparse, irregularly distributed rough endoplasmic reticulum. Another type of neurone, characterized by a smooth nuclear envelope and a dense cytoplasm with a regular rough endoplasmic reticulum, on the other hand, was seen only rarely after the 6-OH-DA injection, but was the most frequent type in the zona compacta of the control side. It is concluded that this latter type corresponds to the nigral DA neurones. Cell bodies in the zona reticulata mostly seemed completely unaffected. Occasionally (in a recent series of experiments 2 out of 17) the 6-OH-DA injection caused a comparatively large unspecific lesion of about 1 mm in diameter surrounding the site of injection including all cellular elements. Two months after the injection a reduced number of cell bodies were found in the zona compacta. In the striatum the degeneration of nigral cell bodies was followed by a decrease in percentage of boutons with small granular vesicles (as revealed after incubation of striatal slices with α-methyl-noradrenaline (NA) in combination with KMnO 4 fixation) which constitute about 11% of all boutons in normal rats. This decrease was first observed 18 h after the nigral injection and a maximum decrease was found 48 h after injection at which point less than 1% of all boutons contained granular vesicles. A similar low figure was observed at all subsequent time intervals studied suggesting an irreversible degeneration. At the same time degenerating boutons of the dense type appeared in the striatum reaching a maximum of about 2% of all boutons at 48 h after the injection. These dense boutons rapidly disappeared from the striatum indicating a fast digestion by glial elements. Twenty-four hours after a striatal injection of 6-OH-DA typical dense degenerating boutons could be observed in this area. The percentage of dense boutons was considerably higher than after intranigral injections indicating a more synchronous degeneration. After injections into the ascending dorsal NA bundle swollen unmyelinated axons were seen in this area among the myelinated axons with a normal ultrastructural appearance. These enlarged axons contained increased amounts of microtubules, large granular vesicles and mitochondria in the same way as seen after ligation indicating an arrest of the axonal flow. After intraventricular injections two types of changes were seen. Firstly, dense degenerating boutons could be observed both in the striatal and in the hypothalamic periventricular area. Secondly, markedly enlarged axons containing abundant microtubules, large granular vesicles and mitochondria were seen. The present data indicate that intraventricular as well as intracerebral injections of 6-OH-DA may be a useful tool in elucidating the functional role of central catecholamine (CA) neurones. Only little unspecific damage seems to occur and the extent of this damage is in no way comparable to an electrothermic lesion. Occasionally also a comparatively large unspecific lesion (1 mm) occurs after intracerebral injection of 6-OH-DA. This unspecific tissue destruction caused by 6-OH-DA could also be seen in the incubation experiments where striatal slices were incubated in very high concentrations of 6-OH-DA. Therefore selection of an appropriate concentration of 6-OH-DA as well as careful histological examination of the site of injection have to be carried out in order to control the extent of the lesion caused by the drug." @default.
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• W2023248876 date "1973-10-01" @default.
• W2023248876 modified "2023-10-14" @default.
• W2023248876 title "Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurones: An electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro-striatal dopamine system" @default.
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• W2023248876 doi "https://doi.org/10.1016/0006-8993(73)90791-9" @default.
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