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A Probst

Publications and source records attributed to A Probst.

At least 73 records · Page 4Linked to original sources
PubMed1987

Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: forebrain.

The distribution of muscarinic cholinergic receptors in the human forebrain and cerebellum was studied in detail by quantitative autoradiography using N-[3H]methylscopolamine as a ligand. Only postmortem tissue from patients free of neurological diseases was used in this study. The highest densities of muscarinic cholinergic receptors were found in the striatum, olfactory tubercle and tuberal nuclei of the hypothalamus. Intermediate to high densities were observed in the amygdala, hippocampal formation and cerebral cortex. In the thalamus muscarinic cholinergic receptors were heterogeneously distributed, with densities ranging from very low to intermediate or high. N-[3H]Methylscopolamine binding was low in the hypothalamus, globus pallidus and basal forebrain nuclei, and very low in the cerebellum and white matter tracts. The localization of the putative muscarinic cholinergic receptors subtypes M1 and M2 was analysed in parallel using carbachol and pirenzepine at a single concentration to partially inhibit N-[3H]methylscopolamine binding. Mixed populations of both subtypes were found in all regions. M1 sites were largely predominant in the basal ganglia, amygdala and hippocampus, and constituted the majority of muscarinic cholinergic receptors in the cerebral cortex. M2 sites were preferentially localized in the diencephalon, basal forebrain and cerebellum. In some areas such as the striatum and substantia innominata there was a tendency to lower densities of muscarinic cholinergic receptors with increasing age. In general, we observed a slight decrease in M2 sites in elderly cases. Muscarinic cholinergic receptor concentrations seemed to be reduced following longer postmortem periods. The distribution of acetylcholinesterase was also studied using histochemical methods, and compared with the localization of muscarinic cholinergic receptors and other cholinergic markers. The correlation between the presence of muscarinic cholinergic receptors and the involvement of cholinergic mechanisms in the function of specific brain areas is discussed. Their implication in neurological diseases is also reviewed.

Aging↗
PubMed1987

Serotonin receptors in the human brain--III. Autoradiographic mapping of serotonin-1 receptors.

The anatomical distribution of serotonin-1 receptors in human postmortem brain tissue was studied by quantitative light microscopic autoradiography. [3H]Serotonin was used to label all the subtypes of serotonin-1 sites (serotonin-1A, serotonin-1B, serotonin-1C). Serotonin-1A receptors were specifically labelled with [3H]8-hydroxy-2-[N,N-di-N-propyl-amino]tetralin, while [3H]mesulergine was used to identify serotonin-1C receptors. Receptor densities were quantified by means of a computer-assisted microdensitometric system. Confirming previous findings, serotonin-1A and serotonin-1C receptors were found in the human brain, while sites with the pharmacological characteristics of serotonin-1B binding sites could not be identified in this tissue. In addition, serotonin-1C receptors appeared to present differences in terms of pharmacology, depending on the brain area analysed. The distribution of both serotonin-1A and serotonin-1C receptor subtypes throughout the human brain was heterogeneous. High or very high densities of serotonin-1A receptors were found over the Ca1 field of the hippocampus, raphé nuclei, layers I and II of the cortex and some nuclei of the thalamus and amygdala. The claustrum, posterior hypothalamus, mesencephalic and pontine central grey matter and substantia gelatinosa of the cervical spinal cord, among others, presented intermediate concentrations of serotonin-1A receptors. In contrast, high densities of serotonin-1C receptors were present in the choroid plexus, substantia nigra, globus pallidus and ventromedial hypothalamus, while low or very low amounts of this receptor subtype were found in many other human brain areas. The anatomical distribution of serotonin-1A and serotonin-1C receptors is discussed taking into account the distribution of serotonergic neurons and fibres, the central functions in which serotonin appears to be involved and the characteristics of the neurological and psychiatric disorders where changes in brain serotonin-1 receptors have been reported.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Serotonin receptors in the human brain--IV. Autoradiographic mapping of serotonin-2 receptors.

The anatomical distribution of serotonin-2 receptors in the human brain was studied by light microscopic autoradiography, using [3H]ketanserin as a ligand. The receptor densities were quantified by microdensitometry with the aid of a computer-assisted image-analysis system. A heterogeneous distribution of serotonin-2 receptor densities was found in the human brain. Very high concentrations were localized over layers III and V of several cortical areas, including the frontal, parietal, temporal and occipital lobes, the anterogenual cortex and the entorhinal area, as well as in the corpus mamillare of the hypothalamus. The claustrum, nucleus lateralis of the amygdala and some cortical layers also presented a high density of serotonin-2 receptors. Intermediate concentrations were found over the hippocampus, the caudatus, putamen and accumbens nuclei, and some nuclei of the amygdala, among other structures. Areas such as the thalamus, brain stem, cerebellum and spinal cord contained, in general, only low to very low densities of serotonin-2 receptors. A very high level of non-specific binding, which was not displaceable by any serotonin-2 compound, was found in some areas of the human brain, including the caudatus and putamen nuclei, the substantia nigra and the raphé nuclei. The distribution of serotonin-2 receptors in the human brain described herein is discussed in relation to the distribution of serotonergic innervation, the central effects which have been proposed to be serotonin-2-mediated, and the neuropathological characteristics of the diseases where a modification in the number of serotonin-2 receptors has been reported.

Adult↗
PubMed1987

Adenosine A1 receptors in the human brain: a quantitative autoradiographic study.

The distribution of adenosine A1 receptors in the human brain was studied by autoradiography in post mortem brain tissues from 26 subjects without reported neurological disease. N6-[3H]Cyclohexyl-adenosine was used as the ligand. For comparison, adjacent sections of some regions were examined histochemically for 5'-nucleotidase activity. The receptor sites were heterogeneously distributed throughout the CNS. The highest receptor densities were found in the stratum oriens, pyramidale and radiatum of the hippocampus. High densities were also found in the cerebral cortex and the striatum. In the thalamus there was a heterogeneous distribution of binding sites with a high density in structures such as the medial and anterior nucleus. Intermediate receptor densities were found in the accumbens, the olfactory tubercle and most parts of the amygdala among others. The hypothalamus had low receptor densities. In the brainstem and the spinal cord very low receptor concentrations were found. However, in some structures such as the substantia nigra, the colliculus superior and the substantia gelatinosa of the spinal cord a low level of binding could be measured. The cerebellar cortex showed low densities of receptors. Structures showing high levels of 5'-nucleotidase activity were the hippocampus, the striatum and parts of the cerebral cortex among other regions. In general there was a poor correlation between the localization of A1 receptors and the 5'-nucleotidase activity. Some regions, however, showed a similar distribution of these two markers. In general, the distribution of adenosine A1 receptors found in the human brain is comparable to that found in previous autoradiographic studies in the rat brain. However, some regional differences were observed in, for example, the cerebral cortex, the striatum and the cerebellar cortex. These differences may prove to be functionally relevant.

5'-Nucleotidase↗
PubMed1987

Cytoskeletal immunohistochemistry of Alzheimer's dementia and related diseases. A study with monoclonal antibodies.

Mabs directed against phosphorylated epitopes on the heavy and medium neurofilament protein were used to immunostain histological sections from brains of patients without neurological disease and patients suffering from SDAT, Pick's disease, Parkinson's disease, progressive supranuclear palsy and encephalomalacias of the white matter inducing chromatolysis in the overlying cortex. In normal brains only axons but never perikarya were stained. In the pathological brains, however, swollen neurons with chromatolysis and swollen cells in Pick's disease, NFT in SDAT, Pick bodies in Pick's disease, the centers of Lewy bodies in Parkinson's disease and some tangles in progressive supranuclear palsy were stained. These changes are perikaryal alterations. The results are discussed in relation to the formation of NFT in SDAT, i.e. the PHF as seen by electron microscopy. It is concluded that in spite of the reliable staining of NFT with some of our mabs, with sera directed against PHF, MAPs and other cytoskeletal proteins there is no absolutely specific immunoreaction for PHF. The most similar pattern to that observed in NFTs of SDAT is seen in the Pick bodies of Pick's disease, although these do not consist of PHF when looked at with the electron microscope, and although they behave differently from NFT in some 'conventional' histological stains. From this nonspecificity of the immunoreaction and from the presence of multiple cytoskeletal epitopes in NFT it is concluded that NFT (i.e. PHF) are probably not derived from one particular cytoskeletal element but are reassembled from proteolytic breakdown fragments of several of these elements. In this regard the similarities and dissimilarities with the alterations of Pick's disease might be specially relevant and deserve further studies, especially as the clinical features of SDAT and Pick's disease can be very similar.

Alzheimer Disease↗
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↗