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A Zuddas

Publications and source records attributed to A Zuddas.

30 records · Page 2Linked to original sources
PubMed1990

Early appearance of tyrosine hydroxylase immunoreactive cells in the mesencephalon of mouse embryos.

The development of mesencephalic catecholaminergic neurons in the embryonic and fetal mouse was analysed in tissues fixed with 5% acrolein using polyclonal rabbit antibodies against tyrosine hydroxylase (TH), the first enzyme in catecholamine synthesis. The first TH positive cells were identified as early as day 8.5-9 of gestation and some expressed TH while apparently still migrating from the proliferative layer. The number of catecholamine cells increased dramatically by embryonic day 9.5-10; at gestation days 10.5-11 numerous TH positive cells bearing many neurites were localized in the ventral part of the mesencephalon but they were not yet separated into two different groups (A9 and A10). After 13 days of gestation two separate catecholaminergic groups could be visualized, although many TH positive cells with long neurites (putative dopaminergic neurons) could still be seen at the edges of the ventricle, and appeared to be moving towards the ventral mesencephalon. On the basis of these results the possibility that catecholamine cells that are produced early during the development of the midbrain may have neurotrophic and/or morphogenetic roles is discussed.

Aging↗
PubMed1989

MPTP treatment combined with ethanol or acetaldehyde selectively destroys dopaminergic neurons in mouse substantia nigra.

We have previously reported that ethanol and acetaldehyde potentiate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, enhancing dopamine (DA) depletion in the striatum. The present study was designed to determine whether such enhancement of neurotoxicity was specific for the nigro-striatal DA pathway. In 5-week-old mice acetaldehyde treatment did not enhance DA depletion seen 7 days after MPTP treatment. In 8-week-old animals, however, acetaldehyde or ethanol given with MPTP decreased striatal DA content to about 10% of controls, whereas the depletion was to 43% of controls when MPTP was given alone. In acetaldehyde or ethanol and MPTP-treated mice, changes in DA levels were observed only in the striatum. DA contents in the hypothalamus, olfactory bulb and frontal cortex were similar to that in controls. Contents of norepinephrine and serotonin in striatum, hypothalamus, olfactory bulb and cerebral cortex were not affected by any of the treatments. Three months after MPTP alone, striatal DA recovered to 74% of controls in 8-week-old mice, whereas no recovery occurred in acetaldehyde and MPTP-treated mice. Moreover, both tyrosine hydroxylase (TH) immunocytochemistry and Cresyl violet staining showed an extensive and selective cell loss in the pars compacta of the substantia nigra (SNc) of the mice treated with acetaldehyde or ethanol and MPTP, whereas MPTP alone caused only a limited cell degeneration.

Acetaldehyde↗
PubMed1989

Acetaldehyde directly enhances MPP+ neurotoxicity and delays its elimination from the striatum.

We have previously shown that ethanol and acetaldehyde (ACE) potentiate MPTP toxicity in mice, selectively enhancing dopamine (DA) depletion in the striatum and markedly increasing loss of DA neurons in the substantia nigra. Several months after these combined treatments there is no evidence of any recovery. In the present study, we measured the accumulation of the MPTP toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) in both striatum and whole brain, after MPTP alone or after combined treatments with ethanol or acetaldehyde, in order to determine whether this enhancement of toxicity is caused by changes in the MPTP metabolism. We also investigated whether acetaldehyde interfered with the conversion of MPTP to MPP+ by glial cells in vitro and studied its effects on the MPP+ uptake and spontaneous release from mesencephalic DA neurons or striatal astrocytes in primary cell cultures from E13 mouse embryos. The results from the in vivo experiments indicated that relatively low doses of ethanol or acetaldehyde potentiate directly MPP+ toxicity, apparently without interfering with its pharmacokinetics. However when higher doses of these drugs were administered, they also decreased MPP+ clearance from the striatum. ACE also increased initial MPTP accumulation in the whole brain but failed to enhance MPP+ levels, thus indicating that ACE effect is not related to MPTP metabolism. In vitro studies confirmed that ACE does not modify MPTP metabolism in striatal or mesencephalic astrocytes in culture. In mesencephalic neuronal cultures ACE does not change the levels of MPP+ uptake (MPP+ is accumulated in putative DA neurons in vitro with a mechanism similar to that of the DA high affinity uptake) nor its spontaneous release. These results indicate that the slower MPP+ clearance from the stratum after ACE is not related to a direct effect of ACE on DA neurons or astrocytes.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Covalent protein binding of a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mouse and monkey brain in vitro and in vivo.

We have recently reported that a reactive metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is formed in rat brain in vitro by type B monoamine oxidase (MAO). In the present study, we further characterize the irreversible binding in vitro using tissues from mice and monkeys, two species more sensitive than rats to MPTP neurotoxicity. We also report the occurrence of irreversible binding of radioactivity after administration of tritiated MPTP in the same species in vivo. Tissue homogenates were incubated at 37 degrees with 1-[methyl-3H]MPTP in in vitro experiments. Animals were injected with labeled MPTP and sacrificed at different times in in vivo experiments. The perchloric acid precipitates of tissue homogenates from either procedure were washed exhaustively with organic solvents and counted for radioactivity. The amount of recovered radioactivity in in vitro experiments was similar using brain homogenates from mice and monkeys, whereas a considerably lower amount was found in mouse liver. MAO-B inhibitors decreased the covalent binding. However, the combined MAO-B/MAO-A inhibitor pargyline had no effect if added after 2 hr of incubation. Sulfhydryl-containing compounds decreased the covalent binding in a concentration-related manner. GSH reduced the rate of the reaction throughout the incubation. The covalent binding slowly increased in time in vivo in mouse brain, not in liver. There was a two-fold variation of covalently bound radioactivity in different brain areas of 3H2-MPTP-treated monkey. This reactive metabolite may play a role in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism and 1-methyl-4-phenylpyridinium uptake in dissociated cell cultures from the embryonic mesencephalon.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a contaminant found in a synthetic illicit drug, can elicit in humans and monkeys a severe extrapyramidal syndrome similar to Parkinson's disease. It also induces alterations of the dopamine (DA) pathways in rodents. MPTP neurotoxicity requires its enzymatic transformation into 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase followed by its concentration into target cells, the DA neurons. Here, we show that mesencephalic glial cells from the mouse embryo can take up MPTP in vitro, transform it into MPP+, and release it into the culture medium. MPTP is not taken up by neurons from either the mesencephalon or the striatum in vitro (8 days in serum-free conditions). However, mesencephalic neurons in culture revealed a high-affinity uptake mechanism for the metabolite MPP+, similar to that for DA. The affinity (Km) for DA uptake is fivefold higher than that for MPP+ (0.2 and 1.1 microM, respectively), whereas the number of uptake sites for MPP+ is double (Vmax = 25 and 55 pmol/mg of protein/min for DA and MPP+, respectively). Mazindol, a DA uptake inhibitor, blocks the uptake of DA and MPP+ equally well under these conditions. Moreover, by competition experiments, the two molecules appear to use the same carrier(s) to enter DA neurons. Small concentrations of MPP+ are also taken up by striatal neurons in vitro. The amount taken up represented less than 10% of the MPP+ uptake in mesencephalic neurons. Depolarization induced by veratridine released comparable proportions of labeled DA and MPP+ from mesencephalic cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice is enhanced by ethanol or acetaldehyde.

Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments (ethanol and MPTP or acetaldehyde and MPTP), the animals exhibited a marked and long-lasting catatonic posture and then returned gradually to apparently normal locomotion. Seven days after MPTP administration, depletion of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum were further potentiated in the group of animals treated with ethanol. This effect was more evident when the treatment was repeated twice and was dose-dependent. Acetaldehyde was more potent than ethanol in enhancing MPTP neurotoxicity. A single exposure to acetaldehyde before and during MPTP treatment produced a very consistent fall of DA, DOPAC and HVA but not serotonin (5HT) or 5-hydroxyindoleacetic acid (5HIAA) in the striatum. This suggests that ethanol effects on MPTP neurotoxicity might be related to acetaldehyde formation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Cluster headache: clinical efficacy of lithium salts in a haemodialysis treated patient.

Over the last ten years the efficacy of lithium salts in cluster headache has been well demonstrated. Our patient, who had been suffering from cluster headache for approximately 30 years, had been in haemodialysis treatment for the last ten years for chronic renal failure. Moreover, he was affected by heart failure and peptic ulcer. The patient was currently under therapy with Digitalis, Isorbide dinitrate, and ranitidine and was dialyzed three times a week for a total of five hours each time. Neither prophylactic headache therapy nor high doses of analgesic drugs had proved effective. Although this patient was in haemodialysis, lithium treatment was indicated. The administration of lithium carbonate 300 mg during dialysis days and 150 mg during non-dialysis days improved the attacks. Complete recovery from the attacks was obtained when the serum levels of lithium reached the therapeutic range. No side effects were noted.

Cluster Headache↗