Biomedical subjects

C Mytilineou

Publications and source records attributed to C Mytilineou.

70 records · Page 4Linked to original sources

PubMed1976

Destruction of sympathetic nerve terminals by 6-hydroxydopamine: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea, diethyldithiocarbamate, methimazole, cysteamine, ethanol and n-butanol.

1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) administered i.p. to mice prevented the neurodegenerative actions of subsequently injected (1 hour later) 6-hydroxydopamine (6-OHDA) or 6-aminodopamine on peripheral adrenergic nerve terminals. Destruction of nerve terminals was studied in vitro in the left atrium by measuring the accumulation of 3H-norepinephrine (3H-HE), and in the iris by both 3H-NE accumulation and fluorescence microscopy methods. Strong protection was observed at 4, 24 and 72 hours after 6-OHDA. The degree of protection was dose-dependent and showed step-wise decrements for concentrations of PTTU below 200 mg/kg (viz., 100, 50 and 20 mg/kg) or concentrations of 6-OHDA-HBr above 7.5 mg/kg (viz., 10, 20 and 50 mg/kg). Protection also fell off at time intervals greater than 1 hour after administration of PTTU (viz., 3 and 5 hours). The appearance (fluorescence microscopy) of the nerve plexus of fully protected mice and the remaining plexus in partially protected mice was essentially normal at 24 hours, except for infrequent large swellings. PTTU proved to be a very effective scavenger of hydroxyl radicals; the formation and scavenging of these radicals was studied by gas chromatography in a system in which the hydroxyl radicals (which were generated during the autoxidation of 6-aminodopamine) gave rise to ethylene, a hydrocarbon gas. Other hydroxyl radical scavengers, namely diethyldithiocarbamate and methimazole, exhibited a protective action on sympathetic nerves in the left atrium; PTTU, diethyldithiocarbamate and methimazole are also recognized as copper chelating compounds. Ethanol, n-butanol and cysteamine, which are well known hydroxyl radical scavengers, also exhibited some degree of protection against 6-OHDA. Blockade of transport of 6-OHDA into sympathetic nerves was ruled out as a protective mechanism by the observation that none of the protective compounds inhibited the accumulation of tritium by the left atrium when 3H-NE was injected in place of 6-OHDA. The mechanism of action for these protective agents has not been definitively established, but scavenging of cytotoxic hydroxyl radicals within neurons may play a significant role.

Animals↗

PubMed1975

Prevention of 6-hydroxydopamine neurotoxicity.

1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) prevented the neurotoxic actions of 6-hydroxydopamine on adrenergic nerves in the mouse atrium and iris. This is the first reported 6-hydroxydopamine antagonist that does not act by blocking uptake of catecholamines into nerve terminals. PTTU also prevented the diabetogenic action of alloxan.

Animals↗

PubMed1975

Dopamine-containing neurons of the substantia nigra and their terminals in the neostriatum.

Tne ultrastructural and fluorescence histochemical characteristics of the mature rabbit substantia nigra and neostriatum have been reviewed as a frame of reference for the developmental study. Biochemical investigations were reported on neostriatal dopamine concentrations and the relative uptake and accumulation of 3H-dopamine by this tissue from fetal to adult stages, to provide quantitative data for correlation with the fluorexcence information. The development of the neurons of the substantia nigra and their axons which project to the neostriatum has been presented from their appearance at day 14 of gestation to their maturation in early postnatal life. The initial bipolar neuroblasts, which develop in the midline of the caudal mesencephalon, are fluorescent as soon as they emerge from the ependymal zone. Their fluorescent axons, which form the nigroneostriatal pathway, reach the telencephalon at day 16 of gestation and ramify extensively in the putamen by day 20, but do not enter the caudate nucleus until several days later. Some of the early fluorescent axonal profiles in the putamen are extremely large. Electron microscopic study of theis stage suggests that the large fluorescent profiles may correspond to axonal growth cones or early synapses. A distinct substantia nigra, pars compacta and reticulata, can be recognized by fluorescence microscopy by day 20 of gestation. Electron microscopy reveals that the young neurons are multipolar with numerous developing dendrites, some of which exhibit early synaptic junctions. The subsequent maturaition of these cells and the neuropil is described. The fluorescent axons of the substantia nigra grow into the putamen and caudate nucleus in a nonuniform manner forming fluorescent islands throughout the neostriatum in late fetal life. Occasionally, minute beaded fluorescent axons are found. These profiles might correspond to some of the axons with varicosities "en passage" revealed by electron microscopy. In an attempt to identify further the dopamine-containing axon, the ultratructure of adult neostriatum incubated in 5-hydroxydopamine was reported. Axonal varicosities "en passage" containing a dense "tag" in the vesicles were found. Most of the tagged boutons did not exhibit synaptic contacts. The possible significance of these finding s as related to dopamine secretion are discussed.

Animals↗

PubMed1975

Amphetamine: evaluation of d- and l-isomers as releasing agents and uptake inhibitors for 3H-dopamine and 3H-norepinephrine in slices of rat neostriatum and cerebral cortex.

Release of 3H-doapamine or of 3H-norepinephrine and inhibition of accumulation of 3H-dopamine or 3H-norepinephrine by d- and l-amphetamine were studied in slices of rat neostriatum and in slices of rat cerebral cortex. The two stereoisomers of amphetamine were equally potent as inhibitors of accumulation in the cortex, whereas d-amphetamine was approximately 3-fold more potent than l-amphetamine in the neostriatum. A similar relationship was observed between the two stereoisomers in release experiments. Some spontaneous efflux of 3H-dopamine from tissue slices was evident in absence of added drug in release experiments. When cocaine (2 X 10(-5) M), a known inhibitor of biogenic amine uptake, was added to the medium, there was very little increment in spontaneous efflux of 3H-dopamine in neostriatal slices, but cocaine blocked the release caused by d-amphetamine. This showed that the apparent releasing action of d-amphetamine in the neostriatum was not due to blockade of reuptake of spontaneously released material and that d-amphetamine itself must be taken up to evoke a releasing action. Experiments were designed to compare directly the releasing and uptake inhibiting actions of d-amphetamine. In the cortex, uptake inhibition of 3H-norepinephrine was greater than release over a wide concentration range, while in the neostriatum the two actions were essentially identical in magnitude for 3H-dopamine. We conclude that in the cortex, d-amphetamine can act both to release and to block uptake of 3H-norepinephrine. In the neostriatum, on the other hand, there is releasing action of 3H-dopamine by d-amphetamine (which is stronger than that in the cortex), but the apparent blockade of "uptake" is of questionable significance and appears to result from the release of previously accumulated 3H-dopamine

Amphetamine↗

PubMed1975