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A Probst

Publications and source records attributed to A Probst.

At least 181 records · Page 10Linked to original sources
PubMed1987

Receptor plasticity in the human brain: some autoradiographic studies.

Receptor modifications in human postmortem material were studied by quantitative autoradiography. Alterations of several neurotransmitter receptors in neurodegenerative diseases such as senile dementia and Huntington's chorea, in lesions of specific brain pathways, like the visual pathway or after drug treatments, were examined. In all these situations alterions of the density or localization of receptors were seen using autoradiography. The results suggest that several mechanisms of receptor adaptation operate in the human brain. These mechanisms include: compensatory changes in receptor density as a consequence of cell loss, in some cases preceding the neuropathological changes; differential alterations in receptors depending on their location in a given pathway, for example in the visual pathway or selective homologous or heterologous modification of receptors after drug treatment.

Antidepressive Agents↗
PubMed1987

Neurofibrillary tangles and the neuronal cytoskeleton.

Antibodies to neurofilaments and the microtubule-associated protein, tau, have been used with anti-paired helical filament (PHF) serum to study Alzheimer neurofibrillary tangles. Tangles and their constituent PHF contain epitopes derived from or cross-reactive with both neurofilaments and tau proteins. These same structures are labelled with anti-PHF antibodies. A component of the anti-PHF serum is against tau proteins. We conclude that PHF are at least in part derived from an abnormal neuronal cytoskeleton.

Alzheimer Disease↗
PubMed1987

Cytoskeletal immunohistochemistry of Alzheimer's disease.

The first half of this paper is devoted to a review on the cytoskeletal immunocytochemistry of the various morphological changes in Alzheimer's disease (AD), i.e. neurofibrillary tangles (NFT), senile plaques (SP), granulovacuolar degeneration (GV) and Hirano bodies (HB). In the second half it is demonstrated that sera raised against the paired helical filaments (PHF) in NFT, and monoclonal antibodies to phosphorylated epitopes on neurofilament proteins, also stain structures within neuronal perikarya without PHFs in some diseases. These include Pick bodies and swollen cells in Pick's disease, neurons in old dogs without NFTs, and occasional neurons without NFT in AD. We conclude that PHF constituent proteins can be accumulated in neuronal perikarya of cases with these diseases without being actually assembled to PHFs. In AD and in the old dogs, such accumulations occurring without the formation of PHFs might represent a precursor state of the latter.

Alzheimer Disease↗
PubMed1986

Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites.

The presence, pharmacological properties and anatomical distribution of serotonin-1A and serotonin-1B receptor subtypes were studied in the human brain by both radioligand binding assays and autoradiographic procedures. Frontal cortices and hippocampi from human brains obtained at autopsy without evidence of neurological disease were used in this study. [3H]5-HT was used to label both 5-HT1A and 5-HT1B receptor subtypes. 5-HT1A receptors were selectively labeled by [3H]8-hydroxy-2[di-N-propylamino]tetralin, while 5-HT1B receptors were labeled by (-)-[125I]iodocyanopindolol ([125I]CYP) in the presence of 30 microM isoprenaline. The pharmacological profile of 5-HT1A receptors in human brain tissue was very similar to those previously found in rat and pig brain tissues. The general anatomical distribution of these sites was also similar to that found in the rat brain, although some differences were observed when analyzed at the microscopic level. In contrast to 5-HT1A receptors, it was not possible to identify 5-HT receptors having the pharmacological properties of 5-HT1B sites in the human brain, using either [3H]5-HT or [125I]CYP as ligands. The absence of identifiable 5-HT1B receptors in human brain preparations, a fact previously found in pig brain tissue, is discussed in terms of the existence of species differences in brain serotonin receptors.

Aged↗
PubMed1986

Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites.

The presence, pharmacological properties and anatomical distribution of serotonin-1C and serotonin-2 receptor subtypes were studied in the human brain by both radioligand binding and autoradiographic procedures. Frontal cortex, hippocampus and choroid plexus from human brains obtained at autopsy without history of neurological diseases were used in this study. [3H]5-HT and [3H]mesulergine were used to label 5-HT1C recognition sites while [3H]ketanserin was used to label 5-HT2 receptors. The pharmacological profile of 5-HT1C sites which are very concentrated in the choroid plexus, was extremely similar to that of pig and rat 5-HT1C sites. These receptors were also detected in the hippocampus and the cortex from human brain. The general distribution of 5-HT1C sites in human and rat brain was similar although slight differences were observed. Human 5-HT2 receptors were concentrated in cortical areas but also found in the hippocampus. The pharmacological profile of these receptors was extremely similar in human and pig brain tissue, but differed in certain respects to that found in rat brain 5-HT2 receptors. The anatomical distribution of 5-HT2 receptors is similar in human and rat brain with some differences at the microscopic level. The importance of species differences in the development of 5-HT2 compounds is discussed.

Aged↗
PubMed1986

'Peripheral' benzodiazepine binding sites in human brain and kidney: autoradiographic studies.

Benzodiazepine (BZ) recognition sites of the 'peripheral' type were localized autoradiographically in human postmortem brain and kidney using [3H]Ro 5-4864. These sites presented a relatively homogeneous distribution. Areas such as the ependyma, choroid plexus and olfactory bulb, which in the rat are very rich in these binding sites, presented densities in the human brain which were about 1/10 of those seen in the rat. Human tissues presenting gliosis, such as the hippocampi from senile dementia patients, did not show a clear increase in the number of [3H]Ro 5-4864 sites, in contrast with the high densities found in rat brain areas presenting neurotoxin-induced gliosis. Intermediate densities of binding were seen in a human glioblastoma tumor. The human kidney also showed lower densities of peripheral BZ binding sites, when compared to the rat kidney. These results indicate that marked species differences exist in the densities of peripheral BZ sites and that caution has to be exerted when extrapolating data from the experimental animal to human.

Aged↗
PubMed1986

Adenosine A1-receptors in human brain: characterization and autoradiographic visualization.

The characteristics and distribution of adenosine A1-receptors in human brain tissues were examined, using [3H]N6-cyclohexyladenosine ([3H]CHA) as a ligand. The binding of [3H]CHA had the pharmacological characteristics of an A1-receptor site and was similar to those of adenosine A1-receptors in rat brain tissue examined in parallel. Autoradiographic localization of adenosine A1-receptors in human brain tissues revealed a heterogeneous anatomical distribution with high levels, particularly in the hippocampal formation, striatum, neocortex and some thalamic nuclei. The distribution of receptors was similar to that seen in the rat brain. However, in some regions, as for example the cerebellar cortex, clear differences were seen.

Adenosine↗
PubMed1986

Dementia of Alzheimer type (DAT)--a review of its morbid anatomy.

The most important morphological findings in dementia of Alzheimer type (DAT) are Alzheimer neurofibrillary tangles, senile plaques, amyloid angiopathy, granulovacuolar degeneration and Hirano bodies. The morphological and immunocytochemical findings in these changes are described, in particular those related to the pathological cytoskeleton. Their possible relationship to the disturbed synthesis of neurotransmitters recently demonstrated is considered, and their relevance for the clinical syndrome of dementia is discussed. Hypothetical etiologies (ageing per se, genetics, infection and chronic intoxication) are briefly mentioned.

Aged↗
PubMed1986

Muscarinic cholinergic receptor subtypes in the human brain. II. Quantitative autoradiographic studies.

The distribution and characteristics of M1 and M2 muscarinic cholinergic receptors as defined by their affinity for the antagonist pirenzepine were studied in the human brain using in vitro quantitative autoradiographic techniques. The binding of N-[3H]methylscopolamine ([3H]NMS) to cortical and striatal microtome tissue sections was saturable and presented a Kd of 0.25 nM. The sensitivity of [3H]NMS-binding sites to 100 microM carbachol and 300 nM pirenzepine was analyzed in 30 brain areas. In selected brain regions, complete competition curves using carbachol, pirenzepine and atropine were analyzed. Finally, the regional distribution of M1 sites was studied using [3H]pirenzepine ([3H]PZ) as ligand. The binding of [3H]NMS to striatum, hippocampus and amygdala was very sensitive to pirenzepine but not to carbachol. The opposite situation was found in thalamus, hypothalamus, substantia innominata, pons and medulla, while intermediate sensitivity to both displacers was observed in different layers of the cortex and in the claustrum. Competition experiments showed that [3H]NMS binding was displaced with the same affinity by atropine in all the regions studied, while the IC50 of carbachol varied from 5 microM in the nucleus facialis to 830 microM in the caudate. Pirenzepine IC50 values for [3H]NMS sites varied from 66 nM to 1 microM. Results using [3H]PZ further confirm this pattern of distribution, with high densities of binding observed in the striatum, hippocampus and amygdala and very low in thalamic and brainstem areas. These results show that the putative M1 and M2 muscarinic receptor subtypes present a differential anatomical distribution in the human brain. This differential distribution is comparable to that observed in the rat brain. Some basal ganglia and limbic areas are enriched in M1 sites, while thalamus, brainstem, medulla and also the hypothalamus and substantia innominata contain predominantly receptors of the M2 type. The cerebral cortex is an example of a region containing a mixed population of M1 and M2 sites. These results provide an anatomical description of the distribution of subtypes of the muscarinic receptor in the human brain, which can be related to the known pharmacological effects of muscarinic agents in brain function.

Aged↗
PubMed1986

Alzheimer's paired helical filaments share epitopes with neurofilament side arms.

A panel of monoclonal antibodies to neurofilaments have been investigated with regard to the location of their respective epitopes on neurofilament polypeptides and their ability to label the neurofibrillary tangles and paired helical filaments (PHF) which are characteristic of Alzheimer's disease. All of the neurofilament monoclonal antibodies that label tangles and PHF are directed against epitopes in the side arm domains of the two larger neurofilament polypeptides, NF-H and NF-M, and do not recognise the alpha-helical rod domains of these proteins. Immuno-electron microscopy demonstrates that the neurofilament antibodies label the constituent PHF per se and do not simply stain neurofilaments that might be admixed with PHF. These neurofilament epitopes are differentially retained by PHF, following isolation. Thus, antibody labelling of PHF is not simply due to the presence of normal neurofilament polypeptides. We propose that in tangle-bearing neurons, neurofilaments are degraded by proteases and that it is fragments of the side arms which contribute to the composition of PHF.

Alzheimer Disease↗
PubMed1986

The brain diseases causing senile dementia. A morphological study on 54 consecutive autopsy cases.

Brains from 54 patients with organic dementia were examined systematically. As in previous investigations a predominance of Alzheimer type changes was observed. Seventeen patients showed Lewy bodies in the nucleus basalis, the substantia nigra and the locus coeruleus as well as other lesions of parkinsonian type. In 5 cases these changes were thought to be responsible for dementia. In 8 patients no convincing morphological substrate of dementia was found. These patients were older than average; therefore age per se might have been responsible for dementia. It is emphasized that subjective judgements are almost unavoidable in assessing the cause of organic dementia.

Aged↗
PubMed1986

Distribution of somatostatin receptors in the human brain: an autoradiographic study.

High affinity somatostatin receptors have been measured in postmortem brains from 18 neurologically asymptomatic patients (mean age: 67 years) using the stable somatostatin analog 125I-204-090, DPhe-Cys-Tyr-DTrp-Lys-Thr-Cys-Thr(ol), as radioligand. In homogenates from human frontal cortex, high affinity (Kd = 0.52 nM; Bmax = 557 fmol/mg protein) receptors with pharmacological specificity for somatostatin, [D-Trp8]somatostatin and somatostatin-28 were found. The CNS distribution of these receptors was studied by autoradiography. Somatostatin receptors were distributed in varying densities throughout the whole brain. High concentrations are found in all cortical layers, the deeper layers (V-VI) being usually more dense than the superficial layers (I-III). The limbic system is heavily labeled, in particular hippocampus (CA1, dentate gyrus), most of the nuclei of the amygdala, and the habenula. Also parts of the basal ganglia are very rich in somatostatin receptors: the nucleus caudatus as well as the nucleus accumbens are very dense, whereas the globus pallidus is virtually unlabeled. Interestingly, significant amounts of somatostatin receptors are found in the human cerebellum, which is devoid of endogenous somatostatin. Other discrete areas of the CNS are enriched with somatostatin receptors: locus coeruleus, tuberal nuclei of the hypothalamus, claustum, tuberculum olfactorium as well as spinal trigeminal nucleus and substantia gelatinosa of the spinal cord. The substantia innominata is poor in somatostatin receptors. In general there is a good correlation in the distribution of somatostatin receptors in the human and rat brain and there is a reasonable correlation with endogenous somatostatin levels in human brain tissue, particularly in the larger structures. The very high density and the specific localization of somatostatin receptors in strategic key points in the CNS such as cortex, basal ganglia, limbic system and substantia gelatinosa suggests an important role of somatostatin in cognitive, sensory and extrapyramidal motor functions. The significance of somatostatin receptors in the human cerebellum remains to be elucidated.

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PubMed1986

The distribution of glycine receptors in the human brain. A light microscopic autoradiographic study using [3H]strychnine.

Glycine receptors were localized autoradiographically in postmortem human brain material using [3H]strychnine as a ligand. Slide mounted tissue sections were labeled in vitro by incubation with [3H]strychnine and autoradiograms obtained using [3H]Ultrofilm. Receptor densities were quantified by computer assisted microdensitometry. No specific binding of [3H]strychnine was observed in any of the forebrain areas studied. Low densities were seen in the midbrain except for dorsal and lateral parts of the periaqueductal grey matter and the oculomotor nuclei. In pons, medulla oblongata and upper cervical cord high densities of [3H]strychnine binding sites were associated with some nuclei including the motor and sensory trigeminal nuclei, the facial and the hypoglossal nuclei. The highest densities of grains were associated with the substantia gelatinosa of the trigeminal nucleus in the medulla oblongata. A peculiar spotty distribution of [3H]strychnine binding sites were found in the gracilis and cuneatus nuclei. The distribution of glycine receptors in the human brain is comparable to that seen in the rat brain, although densities are much higher in the rat. The distribution of glycine receptors in the human brain provides an anatomical substrate for the understanding of the effects of drugs acting in these receptors, particularly strychnine.

Accessory Nerve↗
PubMed1986

Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes.

Three monoclonal antibodies to neurofilaments (RT97, BF10 and 147), two of which also recognised neurofibrillary tangles (RT97 and BF10), have all been shown to be specific for phosphorylated epitopes. Treatment of histological sections with alkaline phosphatase prior to immunostaining resulted in reduction of axonal neurofilament staining with all three whilst the neurofibrillary tangles staining with BF10 was unaffected. Antibody 147 was found to recognise weakly some neurofibrillary tangles following alkaline phosphatase treatment. The results presented confirm the presence of structurally abnormal but phosphorylated neurofilaments in neurofibrillary tangles.

Alkaline Phosphatase↗
PubMed1985

Beta-adrenoceptor subtypes in the human brain: autoradiographic localization.

The distribution and characteristics of beta-adrenoceptors in postmortem human brain was studied using quantitative autoradiographic techniques. 125I-Cyanopindolol was used as a ligand. High densities of beta-adrenoceptors were found in the caudate, putamen, different cortical areas and layers and the hippocampal formation. Low densities were present in other areas such as the thalamus, hypothalamus, midbrain and cerebellar cortex. Specific beta 1 and beta 2 antagonists were used to visualize and quantify separately the two subtypes of beta-adrenoceptors. Computer analysis of the competition curves obtained revealed that the putamen was enriched in beta 1 sites while the cerebellum contained predominantly beta 2 adrenoceptors. The regional distribution of beta-adrenoceptor subtypes was found to be similar to that seen in the rat brain.

Aged↗