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J B Sebens

Publications and source records attributed to J B Sebens.

17 recordsLinked to original sources
PubMed1991

Localization of NMDA and AMPA receptors in rat barrel field.

The aim of this study was to assess the distribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-S-methyl-4-isoxazole propionic acid (AMPA) receptors in the barrel field of rat primary somatosensory (SI) cortex using light-microscopic in vitro autoradiography. NMDA receptors were labeled with the competitive antagonist [3H]CGP39653 or with [3H]glycine in the presence of strychnine, and AMPA receptors with [3H]AMPA. In the SI cortex high densities of the NMDA receptor occurred in the supragranular layers and in layer Va. In layer IV high NMDA receptor densities were specifically confined to the barrel hollows. The AMPA binding sites showed less intralaminar variation and no apparent density differences between the barrel hollows and sides in layer IV. It can be concluded that the distribution of NMDA (but not AMPA) receptors in the rat barrel field shows a strong coincidence with the zone of termination of the specific sensory afferents from the ventral posterior nucleus of the dorsal thalamus.

2-Amino-5-phosphonovalerate↗
PubMed1991

Reduction of adenosine A1-receptors in the perforant pathway terminal zone in Alzheimer hippocampus.

The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alzheimer's disease (AD) patients (n = 9) and non-dement controls (n = 3) has been investigated autoradiographically with [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]CPDPX) as the ligand probe. In AD hippocampi binding of [3H]CPDPX was greatly reduced in the outer two thirds of the dentate gyrus molecular layer, likely due to the degeneration of the perforant path. Binding of [3H]CPDPX was not significantly altered in other parts of the AD hippocampus, e.g. the CA1 and the CA3, in spite of a pronounced cellular pathology and reduced N-methyl-D-aspartate (NMDA) receptor densities, assessed as strychnine insensitive [3H]glycine autoradiography. This contrasts with the presumed localization on dendrites of pyramidal neurons of A1 receptors within the CA1 and the CA3.

Adenosine↗
PubMed1990

Loss of dopamine receptors in the olfactory bulb of patients with Alzheimer's disease.

The presence and localization of dopamine D2 receptors was studied by means of in vitro autoradiography with [3H]N-n-propylnorapomorphine in olfactory bulbs obtained postmortem from Alzheimer patients and age-matched controls. It appeared that, in 5 age-matched controls, the greatest density of dopamine D2 receptors was found in the glomerular layer of the bulb. In 6 of 7 Alzheimer patients, the labeling of the glomerular layer was decreased so that glomerular and granular layer did not differ in labeling density. Tangles, as revealed by Thioflavin S staining, were present in all different layers of the bulbus in Alzheimer patients. Observation of Nissl-stained preparations revealed that mitral cell bodies in bulbs of these patients were not present. Since mitral cells are projection neurons with targets in the entorhinal and piriform cortex, the observation of loss of these cells supports the hypothesis of early involvement of the olfactory system in Alzheimer's disease and the spread from the olfactory mucosa and bulb to the cerebral cortex and hippocampus via degeneration of interconnecting neurons. Moreover, in vivo detection of bulbar dopamine receptors might in the future provide a diagnostic tool for the early detection of senile dementia of the Alzheimer type.

Aged↗
PubMed1989

Positron emission tomographical studies of 1-11C-acetoacetate, 2-18F-fluoro-deoxy-D-glucose, and L-1-11C-tyrosine uptake by cat brain with an experimental lesion.

In cat brain with a freezing injury, the uptake of 1-11C-acetoacetate (11C-ACAC), 2-18F-fluorodeoxy-D-glucose (18FDG), and L-1-11C-tyrosine (11C-TYR) was monitored by positron emission tomography following intravenous administration of the tracers, at 1 day, and 1-3 weeks after the injury. The development and further course of the cold-induced oedema was monitored by magnetic resonance imaging. In the fresh (1 day old) lesion there was increased uptake of 11C-ACAC, probably due to release of the restrictive influence of the blood-brain barrier upon passage of the substance into brain. The uptake of 18FDG, which normally occurs by carrier-mediated transport at the barrier, was decreased in the fresh lesion, probably as a result of damage of the carrier mechanism. In the 3 week old lesion 18FDG uptake was still reduced, and 11C-ACAC uptake was still increased, although barrier function to Evans blue had recovered. It is suggested, that the increased 11C-ACAC uptake in the chronic lesion bears upon the proliferation of macrophages and reactive glial cells in the lesion. This is supported by the increased uptake of 11C-TYR in the 2 weeks old lesion, while in the fresh lesion 11C-TYR uptake was unchanged.

Acetoacetates↗
PubMed1988

Regional differences in reappearance of D2-dopamine receptors in the rat caudate-putamen complex after irreversible inactivation.

The reappearance of D2-receptors in the striatum of the rat was studied by autoradiography after in vivo labeling with [3H]N-n-propylnorapomorphine ([3H]NPA) at various time intervals after the inactivation of dopamine receptors by intraperitoneal administration of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Within two days after inactivation the labeling had decreased to 18% of controls. Thereafter, the label reappeared and after 8 days or more reached levels of 80% of that of untreated controls. Autography showed that 4 h after EEDQ treatment no preferential labeling of the striatum can be seen. Five days after EEDQ a slight difference in labeling density between the medial and lateral striatum was detected, whereas after 18 days a prominent lateromedial gradient in silver grain density was seen, resembling the gradient seen without EEDQ treatment. This silver grain gradient is not paralleled by the density of medium-sized neuronal cell bodies. This suggests a difference in synthesis rate of receptors either in other cells than the medium-sized neuron or, alternatively, in otherwise indistinguishable medium-sized neurons. Five days after EEDQ treatment, clusters of silver grains in the lateral striatum were seen. These clusters have a diameter of 150-400 microns and are separated from each other at 200-500 microns. Each cluster may represent newly synthesized receptors of a single neuron (e.g. cholinergic or somatostatinergic interneuron).

Animals↗
PubMed1987

A mosaic-like distribution of dopamine receptors in rat neostriatum and its relationship to striosomes.

The distribution of dopamine receptors in rat neostriatum was determined by means of light microscopic autoradiography of in vivo labeled binding sites for [3H]N-n-propylnorapomorphine and compared with the distribution of acetylcholinesterase histochemical staining. The distribution of dopamine receptors was non-homogeneous and patches of low receptor density were in register with acetylcholinesterase-poor striosomes. This suggests that the distribution pattern of dopamine receptors is specifically related to various input systems.

Acetylcholinesterase↗
PubMed1987

In vivo labeling of dopamine receptors: light microscopic localization at the cellular level by means of dipping autoradiography with the agonist (3H)N-n-propylnorapomorphine.

A convenient method is described for light microscopic autoradiography at the cellular level for the visualization of in vivo labeled dopamine receptors. (3H)N-n-propylnorapomorphine [(3H)NPA] is administered to rats under conditions that are known to give specific and saturable accumulation in the striatum. Seventy minutes after intravenous administration, the brain is rapidly frozen and cut on a cryostate microtome. The sections are treated with formaldehyde vapor, defatted for 1 hour in xylene and dipped in liquid nuclear emulsion, exposed for 2 weeks and developed. Autoradiograms obtained in this way show a high silver grain density over the striatum and a low density over adjacent external capsule and neocortex. There was a sharp delineated boundary between striatum and adjacent external capsule. Since low energy radiation can be quantified in liquid emulsion autoradiograms, we counted silver grains in a number of regions. The distribution of silver grains appeared to be identical with the distribution of radioactive label after similar in vivo administration of (3H)NPA in other studies.

Animals↗
PubMed1987

Relationship between dopamine receptor occupation by spiperone and acetylcholine levels in the rat striatum after long-term haloperidol treatment depends on dopamine innervation.

The effect of chronic neuroleptic treatment on the relationship between the blockade of dopamine (DA) receptors by the neuroleptic drug spiperone and the decline in acetylcholine (ACh) levels was determined in the rat striatum in vivo. In rats, a unilateral lesion of the nigrostriatal pathway was produced with 6-hydroxydopamine. The rats were treated for 6 weeks with haloperidol (twice a day at 1 mg kg-1). Partial and complete receptor occupation was determined with radioactive spiperone (a D2 antagonist), given in various doses of different specific activity 2 h before death. ACh, choline, and radioactivity contents were measured in the same striatum. Following long-term haloperidol treatment, an increase in the maximal number of binding sites for spiperone was found. Virtually identical negative (linear) correlations between striatal ACh content and the number of receptors occupied by spiperone were found in saline- or subchronic haloperidol-treated rats when DA innervation was intact. The slope of the line describing the decrease in ACh content per occupied receptor, however, was much lower in haloperidol-treated rats than in saline-treated animals. After lesioning of the dopaminergic pathway, there was no longer a correlation between the receptor occupation and ACh levels in the striatum. These results show that receptor occupation by a neuroleptic correlates highly with function only when dopaminergic innervation is intact. Also, it appears that there is no fixed number of striatal ACh molecules per DA receptor, and, finally, that in vivo receptor detection methods distinguish differences in receptor density (as do in vitro techniques).

Acetylcholine↗
PubMed1986

Tracer and maximal specific binding of tritiated spiperone or N-n-propylnorapomorphine to quantify dopamine receptors in rat brain regions in vivo.

Specific tracer and maximal specific binding (Bmax) were determined in rat brain regions from radioactivity accumulation after intravenous administration of 3H N-n-propylnorapomorphine (NPA) or 3H spiperone at various specific activities. With NPA the highest Bmax-values (expressed in pmol.g-1 tissue) were found in the striatum (26 pmol.g-1) nucleus accumbens (about 27 pmol.g-1) and the olfactory tubercle (11 pmol.g-1). Saturable NPA binding was also found in the amygdaloid complex, medulla oblongata and inferior colliculi, but not in the frontal cortex. Bmax values for spiperone were high in the striatum (73 pmol.g-1), the nucleus accumbens (48 pmol.g-1), the olfactory tubercle (34 pmol.g-1) and the frontal cortex (18 pmol.g-1). A similar order was found for the tracer contents in these regions. There was no linear relationship between these contents and Bmax values. The possible implications of these findings and usefulness of NPA for brain imaging are discussed.

Animals↗
PubMed1986

In vivo labelling and axonal transport of monoamine oxidase in the rat basal ganglia using radioactive pargyline.

The enzyme monoamine oxidase was labelled in the rat striatum or substantia nigra with locally injected radioactive pargyline. The binding was prevented by a pretreatment with non-radioactive pargyline, or with a combination of clorgyline and deprenyl. Most of the MAO labelled with 3H-pargyline was of the B-type, but also some MAO-A was labelled, as shown in rats pretreated with clorgyline or deprenyl separately. Seven days after the injection of (3H)-pargyline into the striatum a significant labelling was observed in the substantia nigra. This labelling was clorgyline sensitive, indicating type A MAO, and was not present when striatal neurons were destroyed with kainic acid. Labelling of the striatum following 3H-pargyline injection into the substantia nigra was also less in kainate intoxicated striata. Damage of nigral dopamine neurons with 6-hydroxydopamine did not influence the distribution of the label. Thus by using 3H-pargyline, specific labelling and axonal transport of type A MAO in striatal neurons projecting to the substantia nigra was demonstrated.

Animals↗
PubMed1985

Occupation of dopamine receptors by N-n-propylnorapomorphine or spiperone and acetylcholine levels in the rat striatum.

In an attempt to quantify the interactions between dopaminergic and cholinergic processes, the consequences of complete or partial activation (with N-n-propylnorapomorphine) or blockade (with spiperone) of dopamine receptors for the acetylcholine levels in the rat striatum were studied. The number of specific striatal binding sites (receptors) of spiperone was nearly three times that of N-n-propylnorapomorphine (76 and 26 pmol g-1 wet weight, respectively). The agonist produced a significant increase in the striatal levels of acetylcholine, but there was no simple relationship between receptor binding and these levels. A linear negative correlation was found between the striatal levels of acetylcholine and specific spiperone binding, showing that further receptor blockade induces a decrease in acetylcholine levels, which is independent of the receptors already occupied by the antagonist. The results of this study are evidence that one striatal dopamine receptor regulates the metabolism of at least 400 molecules of acetylcholine.

Acetylcholine↗
PubMed1979

Cyclic AMP in the rat cerebral cortex after stimulation of the locus coeruleus: decrease by antidepressant drugs.

The study concerned the effect of repeated treatment with antidepressant drugs on the elevation of cyclic AMP levels in the rat cerebral cortex following electrical stimulation of the locus coeruleus. Some of the tricyclic and tetracyclic antidepressant drugs inhibited the cyclic AMP response. Desmethylimipramine was the most potent (effective when given 5 mg/kg/day for 2 weeks). Imipramine and nomifensine (daily dose 10 mg/kg for 2 weeks) produced slight decreases, while iprindol and clomipramine were ineffective. After 6 weeks of treatment (daily 10 mg/kg) iprindol, clomipramine and mianserin were without effect. The cyclic AMP response was suppressed by higher doses of the latter two drugs (2 weeks, 20 mg/kg/day). These results indicate that tricyclic and tetracyclic antidepressant drugs are able to decrease cerebral noradrenergic neurotransmission of locus coeruleus neurons, as far as this is mediated by cyclic AMP. It is not clear, however, whether such modification is related to the therapeutic action of antidepressant drugs.

Animals↗
PubMed1979

Probenecid-induced increase of 5-hydroxytryptamine synthesis in rat brain, as measured by formation of 5-hydroxytryptophan.

Probenecid blocks the efflux of 5-hydroxyindole acetic acid (5-HIAA) from the central nervous system, and has therefore been used for turnover measurements of central 5-hydroxytryptamine (5-HT). This substance also elevates tryptophan (TP) levels in rat brain. In this investigation, the time courses of probenecid and TP levels in rat serum and brain after administration of probenecid were studied. Maximal levels of probenecid were reached within 15 min, followed by 50% decrease of serum TP and a 40% increase of brain TP. Brain levels of probenecid were about ten times lower than those in serum. Because TP level in brain is an important factor in the control of cerebral 5-HT synthesis, the effects of probenecid on 5-HT formation in rat brain were investigated. By means of the aromatic L-amino acid decarboxylase inhibitors Ro 4-4602 and NSD 1015, an enhancement of TP hydroxylation of about 35% was demonstrated. It was concluded that penetration of probenecid into the brain is very limited and that probenecid, in addition to blocking egress of 5-HIAA from the CNS, stimulates 5-HT synthesis.

5-Hydroxytryptophan↗
PubMed1976

Serum levels of 5-hydroxyindole derivates after administration of L-5-hydroxytryptophan ethyl ester.

Serum levels of 5-hydroxytryptophan ethyl ester, 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HTPE, 5-HTP, 5-HT and 5-HIAA, respectively), were measured after intravenous administration of L-5-HTPE in humans, premedicated with a peripheral decarboxylase inhibitor. Semi-automated methods for the estimation of the 5-hydroxyindole derivatives are described. Only serum levels of 5-HTP and 5-HIAA were found to be increased, indicating that the ethyl ester is rapidly hydrolyzed and that the decarboxylation of 5-HTP is in part inhibited. The levels of 5-HTP increased during the infusion, but dropped rapidly when the intravenous administration was terminated. Serum levels of 5-HIAA remained constant for at least 6 hours, although during the same period the levels of 5-HTP do change markedly. The persistently increased serum levels of 5-HIAA suggests, that this metabolite is formed from the 5-HT stored in peripheral or central tissue. Serum levels of 5-HIAA may therefore be indicative of changes of 5-HT metabolism during drug treatment. Levels of 5-HTP may be used for the estimation of the availability of the ethylester of 5-HTP.

Adult↗