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C Mytilineou

Publications and source records attributed to C Mytilineou.

At least 55 records · Page 3Linked to original sources

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon.

Explants of embryonic rat mesencephalon were grown in organotypic culture. Addition of 10 microM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the culture medium for 4 to 7 days resulted in loss of dopamine cell bodies and fiber outgrowths, as observed by fluorescence histochemistry. At the same time, the cultures showed decreased uptake of tritium-labeled dopamine. However, no signs of generalized toxicity were evident when the explant cultures were viewed by light and phase-contrast microscopy. These results show that MPTP exerts a relatively selective destructive action in dopamine neurons in vitro, similar to the action observed in humans and monkeys in vivo. Pargyline (10 microM), a monoamine oxidase inhibitor, protected the dopamine neurons in the explants. Organotypic cultures provide an experimental model for the study of the properties of MPTP in vitro.

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

Actin-stimulated myosin Mg2+-ATPase inhibition by brain protein.

A low-molecular-weight protein, isolated from bovine brain, inhibits the actin-stimulated Mg-ATPase activity of myosin from striated muscle. This inhibition is probably related to its ability to cause actin to revert from its polymerized to its depolymerized state and to prevent the polymerization of actin. Its effect on the polymeric state of the actin has been demonstrated by viscosity studies. DNase inhibition assay, and electron microscopy. Heavy meromyosin can overcome the effect of the brain protein and stimulate the polymerization of actin. The inhibition of ATPase activity is in part dependent upon the relative amounts of brain protein, actin, and myosin. The apparent molecular weight of the brain protein is approximately 20,000 daltons. It appears to be a heat-labile glycoprotein containing 5-6% carbohydrate.

Actins↗

Explant cultures of dog substantia nigra and striatum: a model for the study of nigro-striatal dopamine neurons.

The development of organotypic co-cultures of substantia nigra and striatum from newborn dog brain was studied. Histofluorescence demonstrated the presence of catecholamine containing neurons in the substantia nigra. These neurons extended fluorescing processes that entered the striatum. High performance liquid chromatography identified the catecholamine as dopamine (DA). The DA was metabolized to homovanillic acid, which was accumulated in the feeding medium. The synthesis of DA was inhibited by the tyrosine hydroxylase inhibitor alpha-methyl tyrosine. The striatal tissue contained DA receptors, which increased during the development of the cultures. Electron microscopy demonstrated the presence of DA containing axons in the striatum; some of the axons established synaptic contacts with small dendritic branches. Several types of neurons could be identified in the striatum by electron microscopy. The presence of GABA in some striatal neurons was indicated by their ability to accumulate exogenous 3H-GABA. These observations suggest that the organotypic nigro-striatal cultures develop several of the characteristics of the same structures in the brain and therefore could be used as a model for the study of the DA containing neurons of the substantia nigra.

Animals↗

The development of the dog nigrostriatal system in organotypic culture.

Portions of the midbrain and the caudate nucleus from newborn dog (1-3 days old) were maintained in explant culture for periods up to 15 weeks. During that time, nerve cells developing in the midbrain explants projected axons into the explants of caudate. Fluorescence microscopic observations indicated that a large number of projective fibers contained catecholamines with many fluorescing terminals visible in caudate explants. Ultrastructural study disclosed synapses in both midbrain and caudate explants. Some axonal profiles in the caudate were compatible with the appearance of catecholaminergic synapses. Neurochemical analysis showed that the nigrostriatal cultures were capable of dopamine uptake and release.

Aging↗

Neurotransmitter analysis of dermal neurofibromas: implications for the pathogenesis and treatment of neurofibromatosis.

We examined 15 dermal neurofibromas from five adults with disseminated neurofibromatosis. All tumors contained axons that reacted for catecholamines and tyrosine hydroxylase on histochemical stains. Assay of tissue homogenates identified norepinephrine as the catecholamine. Assays for dopamine and choline acetyltransferase were negative. Some axonal components of dermal neurofibromas may originate in sympathetic adrenergic neurons. Most dermal neurofibromas do not contain neuronal cell bodies, and some of the axons may maintain functional connections with proximal sympathetic neuronal cell bodies. Sympathetic denervation may therefore affect the growth of these dermal neurofibromas.

Adult↗

Modifications of female sex chromatin (Barr body) in rat neurons after reserpine administration.

3 groups of rats were sacrificed 30 min, 4 h and 24 h after reserpine (10 mg/kg i.p.) injection. Toluidine blue stained sections showed that in the motor neurons of the spinal cord the drug, at 4 h, had induced a migration of the Barr body from the nucleolus to the nuclear membrane and an increase in its size and RNA concentration. From our findings we suggest that reserpine may have an activating role on X-linked genes.

Animals↗

Decentralization of the superior cervical ganglion in neonates impairs the development of the innervation of the iris. A quantitative ultrastructural study.

The superior cervical sympathetic ganglion was decentralized unilaterally by section of the preganglionic chain in 2- or 4-day-old rats. Twenty-one days post-operatively the dilator muscle of the iris was examined electron microscopically. Quantitative estimates demonstrated that there was a reduction both in the numbers of axon bundles and of individual axons in the iris innervated by the deafferented ganglion as compared with its fellow of the contralateral control side.

Animals↗

Protein-rich cytoplasmic bodies of substantia nigra and locus ceruleus. A comparative study in parkinsonian and normal brain.

A histochemical study of substantia nigra and locus ceruleus from postmortem brains showed the presence of small spherical cytoplasmic bodies stained selectively by the anionic phosphotungstic acid-hematoxylin (PTAH) stain at a pH of 2.5. The metachromatic reaction to PTAH indicates that these protein bodies contain a protein rich in free basic amino groups. The protein bodies are localized within the neuronal perikaryon as well as in their dendritic processes. These bodies abundantly present in the substantia nigra and locus ceruleus of normal brains were noticeably reduced or absent in parkinsonian brains. Lewy bodies when present show that their core gives the same metachromatic reaction to PTAH as do the protein bodies. These findings suggest that an abnormality of protein synthesis in the substantia nigra and locus ceruleus of parkinsonian brains may be related to the absence of protein bodies and the formation of Lewy bodies and play a role in pathogenesis of the parkinsonian state.

Aged↗

Studies on the capacity of mazindol and dita to act as uptake inhibitors or releasing agents for 3H-biogenic amines in rat brain tissue slices.

The effects of the anorexic and stimulant agents mazindol and dita on 3H-biogenic amine uptake and release were determined. Mazindol and dita were very potent inhibitors of 3H-norepinephrine uptake into rat brain occipital cortex slices with ED50 values (point of 50% inhibition of uptake) of 1.5 X 10(-9) M and 3.2 X 10(-9) M, respectively. Mazindol (ED50 of 2.8 X 10(-7) M) and dita (ED50 value of 8.5 X 10(-7) M) were also potent inhibitors of 3H-dopamine uptake into rat neostriatal slices and of 3H-serotonin uptake into whole brain slices (ED50 values of 5.5 X 10(-7) M and 5.1 X 10(-7) M for mazindol and dita respectively). Both compounds proved however to be extremely weak releasing agents for the 3H-biogenic amines in the respective brain areas. The effects of mazindol and dita on uptake may help to explain some of their pharmacological properties.

Acetophenones↗

Target organ regulation of sympathetic neuron development.

The role of target organs in the morphological and biochemical development of sympathetic neurons was examined in the neonatal rat. The superior cervical ganglion (SCG) and its end organs, the salivary glands and iris were employed as a model system. Unilateral sialectomy and iridectomy prevented the normal developmental increase in ipsilateral ganglion tyrosine hydroxylase (T-OH) activity, a marker for adrenergic maturation. Enzyme activity remained depressed by approximately 30% for at least 6 months, the longest time tested. Ganglion morphometry was performed to investigate the basis of the abnormal biochemical ontogeny. Target organ removal significantly decreased the number of adrenergic neurons in the Scg by approximately 30%. Total ganglion volume was reduced in a parallel fashion. Thus, end organ extirpation may prevent the biochemical maturation of the SCG by decreasing adrenergic neuron survival. Sialectomy without iridectomy prevented the normal postnatal increase in ganglion T-OH activity, but did not alter iris activity. These observations suggest that target removal prevents the development of only those neurons destined to innervate that organ. In addition to preventing normal adrenergic neuron ontogeny, target extirpation also prevented the normal development of presynaptic choline acetyltransferase activity. Presynaptic ganglion terminal may have failed to mature normally secondary to adrenergic destruction, or may have responded in some other manner to target organ extirpation.

Animals↗

Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons.

To examine the regulation of development of end organ innervation the superior cervical ganglion (SCG), and two of its target organs, the iris and pineal gland, were studied using biochemical and histofluorescent approaches. During postnatal ontogeny the activity of tyrosine hydroxylase (T-OH), which is localized to adrenergic neurons, increased 50-fold in iris, and 34-fold in pineal nerve terminals of the rat. These increases paralleled the in vitro rise in iris [3H]norepinephrine ([3H]NE) uptake, a measure of the presence of functional nerve terminal membrane. These biochemical indices of end organ innervation correlated well with developmental increases in density of innervation, adrenergic ground plexus ramification and nerve fiber fluorescence intensity as determined by fluorescence microscopy. Unilateral transection of the presynaptic cholinergic nerves innervating the SCG in 2-3-day-old rats prevented the normal development of end organ innervation: T-OH activity, [3H]NE uptake, innervation density, plexus ramification and fluorescence intensity failed to develop normally in irides innervated by decentralized ganglia. It is concluded that trans-synaptic factors regulate the maturation of adrenergic nerve terminals, and the development of end organ innervation by SCG.

Animals↗