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C Feuerstein

Publications and source records attributed to C Feuerstein.

71 records · Page 4Linked to original sources
PubMed1984

Time course of the changes in striatal acetylcholine levels induced by pergolide and haloperidol after lesion of the nigrostriatal dopaminergic pathways in the rat.

Lesion of the nigrostriatal dopaminergic pathway in the rat by 6-hydroxydopamine enhances the ability of pergolide to increase striatal acetylcholine levels and prevents the haloperidol-induced decrease in acetylcholine concentrations. This supersensitive response of striatal cholinergic cells is already maximal 6 days after lesion but tends to decrease thereafter. As the time course of the development of the supersensitivity of cholinergic cells differs from that of increased dopamine binding site density, the two are probably not causally related, the former reflecting rather a change occurring beyond the dopamine recognition site.

Acetylcholine↗
PubMed1982

Dissociate destruction of noradrenaline and dopamine descending projections in the thoracic spinal cord of the rat.

Intracisternal administration of 6-hydroxydopamine to male Wistar rats produced a near complete depletion of noradrenaline levels, as measured by a radioenzymatic assay in micropunches sampled from the dorsal, lateral and ventral horns of the thoracic spinal cord. This drastic effect was reversed by pretreatment with desipramine, a pharmacological inhibitor of noradrenergic neuron uptake. Surprisingly, dopamine content was not significantly reduced. The question as to whether such a lack of concomitant dopamine decrease might be inherent to the dopamine assay itself could be answered by the results obtained with both pharmacological (reserpine) treatments and interference determinations in the dopamine assay. The relative potency of 6-hydroxydopamine to destroy noradrenergic and dopaminergic neurons might account for their differential behavior. Conversely, a large midbrain section performed by knife cut could decrease both dopamine and DOPAC (one of its major acid metabolites) in the thoracic lateral horn and partly in the ventral one. The noradrenaline content was not reduced. Results are discussed in light of recently reported data on dopaminergic descending projections to the spinal cord. The lesion procedures presented here seem to provide valuable tools to dissociate noradrenergic from dopaminergic spinal projections, which is necessary for further anatomical and functional studies on these systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Supersensitivity time course of dopamine antagonist binding after nigrostriatal denervation: evidence for early and drastic changes in the rat corpus striatum.

The sensitivity of the [3H]haloperidol binding technique can be greatly increased by focusing tissue sampling on striatal regions where dopaminergic innervation is the richest. Such sampling is provided from pooled microdiscs punched out of 8 serial 500 micrometer thick sections of the rat brain. With these conditions, the density of receptor sites (Bmax) was found to be twice that of the whole striatum, without modification of the apparent dissociation constant (Kd) and of the Hill's slope. Such a procedure applied to rats with complete 6-hydroxydopamine-induced unilateral nigrostriatal lesions showed a moderate decrease in Bmax in the lesioned side up to 6 days after surgery, whereafter the value of Bmax increased progressively up to the thirtieth day, being then 160% over the control value. Conversely, the apparent Kd decreased significantly from the second to the sixth day postsurgery in the lesioned side, and then increased moderately up to the tenth day and drastically from the twenty-first to the thirtieth day. No change was observed in the corresponding intact side. The modifications appeared chronologically compatible with those corresponding to the behavioral denervation supersensitivity, evidencing drastic binding changes as compared with the whole striatum. The unexpected variations in Kd observed were well correlated with those in Bmax, suggesting that the new available binding sites might be of lower affinity. In the light of all these results, a hypothetical model is proposed.

Animals↗
PubMed1981

Identification and distribution of neuroleptic binding sites in the rat spinal cord.

Identification of neuroleptic receptor sites in the rat spinal cord could be achieved by the binding of [3H]haloperidol to membranes taken from the different horns. The use of pooled frozen microdiscs punched from these different spinal cord areas allowed the detection of saturable stereospecific binding, as defined in the presence of (+)- and (-)-butaclamol. Comparison of the binding constants with those obtained in the corpus striatum resulted in similar dissociation constants and Hill's slopes. Maximal binding capacity was quite different, being the greatest in the whole striatum (157 +/- 8 fmol/mg protein) followed by the dorsal horn (56 +/- 3 fmol/mg protein) and the lateral (34 +/- 5 fmol/mg protein) and ventral ones (31 +/- 2 fmol/mg protein). The displacement of the labelled ligand by different dopaminergic and nondopaminergic drugs at various concentrations gave similar results in the whole striatum and the spinal cord, giving further support for the existence of a dopaminergic innervation of the spinal cord and showing that dopaminergic receptor sites are distributed through the different spinal horns, with a maximal density in the dorsal horn--as for dopamine levels. No detectable stereospecific binding could be obtained from the surrounding spinal white matter, even at high tissue concentrations. Owing to poor sensitivity of the binding technique, no stereospecific neuroleptic binding could be demonstrated in the whole spinal cord, even at very high tissue concentration, whereas it could be detected in spinal cord tissue sampled from restricted areas of dense dopaminergic innervation.

Animals↗
PubMed1980

Stereospecific binding of 3H-haloperidol in rat dorsal spinal cord.

[3H]Haloperidol as dopaminergic ligand used on pooled microdiscs punched from the rat dorsal spinal cord allowed detection of a stereospecific binding. Characteristics of such a binding: dissociation constant, Hill's slope and IC50 of different specific drugs were nearly the same as those found in the striatum, which suggests the presence of individualized dopaminergic receptor sites in the rat dorsal horn. Their density (Bmax) is about three times lower than in the whole striatum.

Animals↗
PubMed1979

Routine identification and determination of 11 barbiturates in biological samples.

A very easy, reliable and specific gas-chromatographic method for identification and dosage of 11 barbiturates in plasma is presented. Methylene unit values determined on two types of column (one polar, one non-polar) allows very accurate identification with a minimum risk of error due to fluctuations in operating conditions. Sensitivity of the method is 0.5 microgram/ml plasma with a flame ionization detector. Derivatization procedure is complete, without any degradation phenomenon as tested by mass spectrometry. Such a method can be easily used as routine procedure for toxicological or pharmacological applications.

Barbiturates↗
PubMed1977

Does O-methyl-dopa play a role in levodopa-induced dyskinesias?

Clinically scored levodopa-induced dyskinesias were correlated with plasma dopa and O-methyl-dopa levels determined every hour during one day in 30 Parkinsonian-treated patients. In patients treated with a combination of L-dopa and a peripheral decarboxylase inhibitor (PDI), those with dyskinesias have very high plasma O-methyl-dopa levels compared with those who have no dyskinesias. In contrast, no significantly different plasma dopa levels are found in these two subgroups of patients, leaving open the question of the possible involvement of such elevated plasma O-methyl-dopa levels in favouring dyskinesias.

Adult↗
PubMed1977

Plasma O-methyldopa in levodopa-induced dyskinesias. A bioclinical investigation.

The peripheral metabolism of Dopa has been studied in correlation with the clinical occurrence of Leyodopa-induced dyskinesias in Parkinson patients. Within the group of patients treated with a peripheral decarboxylase inhibitor (PDI), the combination of all the plasma levels of O-Methyldopa from patients with dyskinesias shows significantly higher values than those from patients without dyskinesias. For Dopa itself, no significant differnece can be detected. Such high O-Methyldopa levels seem to be due to a progressive accumulation of this compound and not to a higher degree of formation. In contrast, no significantly different Dopa or O-Methyldopa levels are found within the group of patients treated with L-Dopa alone. These results are discussed in relation to some of the suspected mechanisms involved in Levodopa-induced dyskinesias.

Aged↗
PubMed1977

[Results of determination of plasma methoxydopa in parkinsonian patients with or without dyskinesia induced by L-Dopa].

Horary plasmatic dosages of Dopa and metabolites in 30 treated parkinsonian patients have shown that, within the group of patients treated with L-Dopa combined with an extracerebral decarboxylase inhibitor, highly significant by increased plasmatic O-methyl-dopa levels can be found in patients with dyskinesias compared with those without dyskinesias. On the contrary, in these two subgroups of patients, plasmatic Dopa levels are not significantly different. By comparing some favoured Dopa and O-methyl-dopa levels between these two subgroups of patients, it seems more likely, that the elevated plasmatic O-methyl-dopa levels are due to an progressive accumulation on of its compound than to an excessive formation from Dopa.

Aged↗
PubMedDate not supplied

Histofluorescence analysis of several systems of catecholaminergic nerve fibres within the rat neostriatum revealed by either restricted lesions of the substantia nigra or gamma-hydroxybutyrate.

The glyoxylic acid fluorescence technique was applied to the study of catecholamine fibres in the caudate-putamen (neostriatum) of control and experimental adult rats. Cryostat or vibratome sectioning procedures were used; in the last case, either incubations of brain slices in gamma-methyl-noradrenaline or pre-treatment of animals with gamma-hydroxybutyrate were performed, in order to increase the intensity of fluorescence. In control animals and in the contralateral side of rats lesioned in the substantia nigra, the fluorescence of the dense plexus of dopamine nerve fibres appeared under the form of densely packed varicosities. However, some regions differed from the ordinary fluorescence of the neostriatum by their stronger intensity and more visible varicosities. They were located principally in the ventro-medial regions bordering either the nucleus accumbens, the dorsal nucleus interstitialis striae terminalis and the ventricle in the anterior part, or the amygdala, the globus pallidus and the ventricle in the posterior part. Moreover, islands of stronger fluorescence also were observed in the head of the caudate-putamen along the dorsal and lateral corpus callosum, as well as scattered in the central region. These particular neostriatal structures might correspond to a separate system of ascending dopamine nerve fibres. Therefore, restricted electrolytic lesions of the substantia nigra pars compacta were undertaken in order to study the morphology of the remaining catecholaminergic fibres in the ipsilateral neostriatum. In largely denervated areas, different types of fluorescent axons were evident. Presumed noradrenergic nerve fibres characterized by a very coarse appearance and closed varicosities were rare. They contrasted markedly with numerous delicate fibres which might belong to several dopaminergic systems. Both first types exhibited long, clearly visible intervaricose segments and ovoid triangular varicosities. The second type, which was thicker and more strongly fluorescent, probably formed the islands observed in unlesioned striata. The third type had very closed, small spherical varicosities and poorly fluorescent intervaricose segments. Dopamine nerve fibres of the same morphology were described previously in the neocortex [43,44] and the possibility of a common origin for nerve fibres of the same type is discussed. When rats were treated with the anaesthetic gamma-hydroxybutyrate, all the dopamine nerve fibres appeared to develop a strong fluorescence within the neostriatum, but more fluorescent islands were always visible. Additionally, some swollen fluorescent fibres were seen; these could be abnormal dopamine fibres whose metabolism had been pathologically altered by the drug.

Animals↗
PubMedDate not supplied

Immunohistochemical study of the catecholaminergic innervation of the spinal cord of the rat using specific antibodies against dopamine and noradrenaline.

We have assessed the relative contributions of dopaminergic and noradrenergic descending systems to the catecholaminergic innervation of the rat spinal cord. Fibres and terminals were labelled with their own neurotransmitter by using specific antibodies raised against dopamine (DA) and noradrenaline (NA) respectively. For this purpose, immunohistochemistry according to the peroxidase anti-peroxidase technique was performed in different experimental conditions. Two group of rats received intracisternal 6-hydroxy-dopamine (6-OHDA) injections either with or without benzatropine pretreatment. Animals of a third group were not pretreated at all. While 6-OHDA induced a complete disappearance of spinal NA-like immunoreactivity (NA-LI), except for scarce residual fibres in the thoracic intermedio-lateral cell column, DA-like immunoreactivity (DA-LI) was unaffected by the lesion. This strongly suggests that the antisera used specifically labelled NA-containing and DA-containing fibres respectively. Spinal DA-LI and NA-LI innervations differed markedly in their topographical distributions and in the morphology of the corresponding fibres. DA-LI innervation was restricted to laminae I, III and IV and to the intermediate zone, especially the autonomic areas. In the ventral horn, it was sparse and more visible after acidification of the fixation solution. NA-LI innervation was much more widely spread. In addition, the organization of NA-LI fibres suggests that the innervation of the whole dorsal horn comes from a group of fibres travelling, at least partially, in the superficial dorsal horn.

Adrenergic Fibers↗
PubMedDate not supplied

[Myoclonic type of Huntington's chorea (author's transl)].

The authors report the case of an 8 year-old boy who, when he was 2 1/2 years old, suffered from spasmodic mouth twitches. At the age of four, various other symptoms appeared: psychomotor backwardness, frequent fails and a photomyoclonic response on electroencephalogram. At the age of 5 1/2, noticeable difficulties appeared in walking with a broad-based gait, hypotonia, and intentional trembling associated with hypokinesia and dysarthria. When he was six, the first convulsive seizure appeared, then myoclonies which became continuous. The child gradually became bedridden. The family history tends to show these disorders can be linked with a Huntington chorea affecting six generations. This case is very similar to that previously described by the authors, in an 8 year-old girl where an anatomic examination revealed the existence of lesions characteristic of Huntington's disease associated with lesions of the cerebellum. The authors, on the basis of the data provided by the literature, discuss the myoclonic and cerebellous aspect of this infantile form. Lacking anatomic evidence, they stress the interest of the biochemical disturbances affecting the cerebral monoamines noted in this observation.

Brain↗
PubMedDate not supplied

Evidence for the existence of L-dopa- and dopamine-immunoreactive nerve cell bodies in the caudal part of the dorsal motor nucleus of the vagus nerve.

The precise neurochemical nature of tyrosine hydroxylase-immunoreactive neurons lying in the caudal part of the dorsal motor nucleus of the vagus nerve of the rat has been identified by immunohistochemistry of the catecholamines themselves. This region corresponds precisely to the area where tyrosine hydroxylase has been previously shown to be colocalized with choline acetyltransferase. Adjacent serial cryostat sections from the medulla oblongata and from the cervical spinal cord were treated either for choline acetyltransferase immunohistochemistry, aromatic L-amino acid decarboxylase and tyrosine hydroxylase immunolabelling or for tyrosine hydroxylase, dopamine, noradrenaline and L-dihydroxyphenylalanine (DOPA) immunostaining. The procedure involved the peroxidase-antiperoxidase method and an intensified diaminobenzidine reaction with imidazole. While no noradrenaline-positive cells were detectable in the dorsal motor vagal nucleus, tyrosine hydroxylase-, dopamine- and DOPA-immunoreactive perikarya were seen in the medial half of this nucleus, caudally the obex level. These results led us to conclude that these tyrosine hydroxylase-positive cells were effectively of dopaminergic nature and therefore that dopamine is a neurotransmitter contained in some neurons of the dorsal motor vagal nucleus. In the light of previous data showing colocalization of tyrosine hydroxylase and choline acetyltransferase in neurons of this portion of the nucleus, colocalization of dopamine with acetylcholine appears most likely. This might shed some light on the physiological consequences of dopamine action at target parasympathetic organs, such as the gastrointestinal tract.

Animals↗
PubMedDate not supplied

[The spinal dopaminergic system].

A new dopaminergic innervation has been described quite recently: the dopaminergic spinal cord system. In this review are presented the different steps which lead to the individualization of this dopaminergic system and the reported results actually available concerning its probable anatomical organization. Finally, most of the data which illustrate the possible functions of this system are discussed. Interestingly, its participation in the transmission of nociceptive signals and the control of cardiovascular patterns appear now well established. Such functional implications give new information on the possible targets of central dopaminergic agonists and antagonists, particularly at the cardiovascular level.

Animals↗
PubMedDate not supplied

[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].

This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.

Dihydroxyphenylalanine↗