Search PubMed⌕ Search

Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

At least 433 records · Page 24Linked to original sources
PubMed1987

Histochemistry of MAO-A and MAO-B in the locus coeruleus of the Mongolian gerbil.

A coupled peroxidation technique for localization of monoamine oxidase (MAO-A and MAO-B), applied to post-mortem fixed tissue of the locus coeruleus of the Mongolian gerbil is demonstrated. Tyramine hydrochloride, beta-phenylethylamine and 5-hydroxytryptamine creatinine sulphate were used as substrates, 1-deprenyl and clorgyline served as specific inhibitors. All three substrates stained the neurons of locus coeruleus in the absence of inhibitor. In the presence of 1-deprenyl, tyramine hydrochloride and 5-hydroxytryptamine creatinine sulphate were metabolized, whereas in the presence of clorgyline no reaction with either substrate could be observed. Immunocytochemical staining of tyrosine hydroxylase (TH) was employed as comparison.

Animals↗
PubMed1987

Reduced concentrations and increased metabolism of biogenic amines in a single case of Rett-syndrome: a postmortem brain study.

Preliminary data of a postmortem brain study in a single case with Rett-syndrome compared to a single control case show a severe reduction of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) in most regions studied and in two regions of adrenaline (A). A marked increase in the 3,4-dihydroxyphenyl acetic acid (DOPAC)/DA, homovanillic acid (HVA)/DA, and the 5-hydroxyindole acetic acid (5-HIAA)/5-HT ratios indicates increased metabolism of DA and 5-HT. Also a marked reduction of 3H-spiroperidol-binding in putamen was found. This agrees with the assumption that a defect in maturation processes of central monoaminergic systems could be an underlying cause of Rett-syndrome.

Biogenic Amines↗
PubMed1987

Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases.

Because dopamine D2 receptors are known to be elevated in schizophrenic brain striata, this study examined whether a similar dopamine receptor elevation occurred in other diseases including neuroleptic-treated Alzheimer's and Huntington's diseases. The average D1 density in postmortem striata from Alzheimer's patients was 17.6 +/- 0.1 pmol/g, similar to an age-matched control density of 16.6 +/- 0.4 pmol/g. The average D1 density in schizophrenia patients was 19.0 +/- 0.6 pmol/g, similar to the age-matched control density of 17.9 +/- 0.6 pmol/g. In Parkinson's disease patients, however, the D1 receptor density was elevated, with values of 22.8 +/- 1.2 pmol/g (in patients not receiving L-DOPA) and 19.6 +/- 1.5 pmol/g (in patients receiving L-DOPA) compared to the age-matched control density of 16.0 +/- 0.4 pmol/g. The D2 receptors in Alzheimer's striata averaged 13.4 +/- 0.6 pmol/g (in patients who had not received neuroleptics), almost identical to the control density of 12.7 +/- 0.3 pmol/g. The average D2 density in neuroleptic-treated Alzheimer's striata was 16.7 +/- 0.7 pmol/g, an elevation of 31%, the individual values of which had a normal distribution. In Parkinson's disease patients, the D2 densities were elevated in tissues from patients not receiving L-DOPA (19.9 +/- 1.5 pmol/g in putamen and 14.8 +/- 1.2 pmol/g in striatum) compared to the age-matched control values of 13.0 +/- 0.4 pmol/g and 12.6 +/- 0.3 pmol/g, respectively. In Huntington's disease patients, the D2 density averaged 7.5 +/- 0.4 pmol/g in patients who had not received neuroleptics, but was 10.3 +/- 0.6 pmol/g in those who had. Although all of the D1 and D2 densities in each of the above diseases and subgroups revealed a normal distribution pattern, the D2 densities in schizophrenia displayed a bimodal distribution pattern, with 48 striata having a mode at 14 pmol/g, and the other 44 striata having a mode at 26 pmol/g. Thus, compared to the neuroleptic-induced and unimodal elevations in D2 of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appear to contain more D2 receptors than can be accounted for by the neuroleptic administration alone.

Adult↗
PubMed1987

Serum iron status in Rett syndrome.

Low ferritin content in putamen and frontal cortex found in a postmortem study in a single case of Rett syndrome prompted measurement of iron-related parameters in blood. Serum ferritin, serum iron and transferrin were evaluated in 27 patients with classical Rett syndrome. Signs of iron deficiency and depletion of body iron stores were found in 20% of probands aged up to 6 years and in 37% older than 14 years. This result is in accordance with figures from the normal female population and therefore a linkage between iron depletion in brain and depleted iron stores could not be proven.

Adolescent↗
PubMed1987

Biochemical aspects of dysphoria: case study for hypothesis generation.

Comparing the pattern of serotonin, 5-hydroxyindole acetic acid, 3,4-dihydroxyphenyl acetic acid and homovanillic acid in five brain areas of one dysphoric patient to those of 3 depressed patients it seems that dysphoria biochemically is a state between depression and mania. Dynamically, dysphoria may possibly be seen as a behavioral correlate of a switch process between high and low turnover of neurotransmitters (rather high frequency in comparison to bipolar disorder with very low frequency). However, the biochemical data are obviously in agreement with psychiatric findings, i.e. that dysphoria in any case is an extremely labile state.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Localization of MAO-A and MAO-B in human brain: a step in understanding the therapeutic action of L-deprenyl.

The discovery that MAO can be differentiated biochemically and pharmacologically into two forms, types A and B, with different substrate specificities and inhibitor sensitivities has renewed the interest in MAO inhibiting as a therapeutic agent. L-Deprenyl, a selective inhibitor of MAO-B, was introduced by us into clinical use as an adjunct to L-DOPA some years ago. This drug has found therapeutic importance in that it can potentiate the pharmacological action of L-DOPA. The mechanism underlying the action of L-deprenyl is thought to be related to its inhibition of MAO-B and thus increased levels of PEA and DA, as measured in the striatal and limbic region of human brain. Animal studies have indicated the MAO-A is mainly, but not exclusively, located in brain neurons, while MAO-B is preferentially placed in glia and astrocytes. In general human and primate brain studies show similar MAO distribution. The observation that MAO-B activity could not be located in the catecholaminergic neurons of human brain by the use of monoclonal antibody studies seriously questions the validity of this technique. The exact locations of MAO-A and -B in human brain are important to understand the mechanism of L-deprenyl action as an antiparkinson drug. If there is an absence of MAO-B from dopaminergic neurons, one may now consider that MAO-B activity within glia plays a far more important role than hitherto considered. This, however, is questionable.

Animals↗
PubMed1987

Cellular action of MAO inhibitors.

Sites of action of monoamine oxidase (MAO) inhibitors in the human brain were analyzed by studying the distribution of the respective MAO subtype, MAO-A or -B. Blood brain barrier (BBB), glial cells and neurons of several brain areas were examined with biochemical and immunocytochemical methods. Whereas MAO-A was localized in microvessels and neurons of locus ceruleus, MAO-B was present predominantly in neuronal cells of dorsal raphe nucleus. The neurons of substantia nigra revealed no immunohistochemically detectable MAO. Astrocytes expressed both subtypes and were observed in all cortical areas examined and all over the brain stem including medulla reticular formation, pontine reticular formation, reticular formation of mesencephalon, midbrain reticular formation, red nucleus, substantia nigra, caudate nucleus and putamen (sections according to DeArmond et al., 1976). MAO activity in several brain areas seems mostly to be due to astrocytes rather than to neuronal cells. As MAO inhibitors have beneficial effects in the treatment of malfunctions of aminergic transmitter systems (Johnstone and Marsh, 1973; Robinson et al., 1973; Birkmayer et al., 1977; Knoll, 1981; Zarifian, 1984; Riederer and Youdim, 1986) and a large amount of MAO activity seems to be localized in brain astrocytes, the function of glial cells especially with regard to their neuromodulating capacity should be focused in more detailed research in future.

Aged↗
PubMed1987

[Changes in organic acids in plasma and cerebrospinal fluid in cerebral infarct].

Seventeen patients with recent cerebral infarction were included in the study. The general condition of the patients was evaluated within 3 days after the incidence (rating 1) and 7-9 days after the incidence (rating 2) using a clinical rating scale for internal, psychiatric and neurological findings. The statistical evaluation showed a clinical improvement of the score of 32%. The extent of the brain lesions was determined by cranial computed tomography. Routine analysis of the cerebrospinal fluid included determination of protein, cell count, cell type, glucose, lactic acid, and hemoglobin. In addition, spinal fluid and serum concentration of pyruvic acid, citric acid, fumaric acid, alpha-ketoglutaric acid and alpha-keto-beta-methylvaleric acid (3-MKV) were determined at the two rating times. CSF and serum values of fumaric acid, 3-MKV and pyruvic acid correlated at rating 1, while at rating 2 a correlation existed only for fumaric acid. A trend analysis infarction - postinfarction period showed the concentration of all metabolites to decrease significantly. This is interpreted as a reconstitution of the initially disturbed blood brain barrier function.

Aged↗
PubMed1987

Terguride: partial dopamine agonist in the treatment of Parkinson's disease.

In an open trial, 15 patients with PD (mostly stage V) were treated with the partial DA agonist, terguride, a derivative of lisuride. To the basic therapy, consisting of L-dopa plus benserazide and amantadine, a slowly increasing dosage of TDHL up to a maximum of 1.5 mg/day t.i.d. was added. There were 3 drop-outs; 12 patients completed the trial which lasted for 12 weeks. At this time a significant improvement in total score, bradykinesia, and functional score was seen, as well as a marked improvement in tremors score in the patients who showed this symptom (Columbia Rating Scale). As side-effects, dyskinesias occurred in two patients, psychotic symptoms in one, and marked orthostatic symptoms in one patient. No significant differences before and after 12 weeks TDHL treatment were found in the concentrations of noradrenaline, adrenaline, serotonin, and 5-hydroxy-indole-acetic-acid in plasma. It is concluded that TDHL is effective even in advanced stages of PD, and it is speculated that partial DA agonists may become important in the treatment of PD and might possibly have an advantage over "classical" DA agonists.

Aged↗
PubMed1986

[Neurobiologic and pharmacologic studies on the pathogenesis of Parkinson disease].

Parkinson's disease is characterized especially by a degeneration of pigmented brain regions, like substantia nigra. These changes are accompanied by a variety of biochemical disturbances of dopaminergic and noradrenergic systems. Also the reduction of serotonin can be related to degenerative processes occurring in subareas of the raphe. Furthermore amino acid transmitters like GABA and a variety of peptidergic neuromodulators are changed. Additional cholinergic hypofunction due to degeneration of the nucleus basalis Meynert is able to impair the quality of life due to loss of intellectual capacity. A variety of biochemical mechanisms compensate for a long time the progression of neuronal loss. Modern treatment strategies (combined L-dopa therapy, dopaminergic agonists, MAO-B inhibitors, amantadine) are able to substitute the deficiency especially of the catecholamines. For the development of more causal therapies, a new animal model has been developed 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism after peripheral administration and leads to denervation of the dopaminergic nigrostriatal system. It is the hope that this new model, which is described here in detail, will lead to decisive data underlying the cause of Parkinson's disease.

1-Methyl-4-phenylpyridinium↗
PubMed1986

Preliminary brain autopsy findings in progredient Rett syndrome.

Postmortem human brain analyses have been performed to further evaluate pathogenetic aspects of the Rett syndrome. While there are no significant abnormalities with respect to amino acid concentrations in putamen, caudate nucleus, red nucleus and thalamus, the concentration of kynurenine is increased in putamen, caudate nucleus, gl. pallidus, raphe and amygdaloid n. In contrast, serotonin and its metabolite 5-hydroxyindole acetic acid are below normal levels. D2-receptor number is decreased and there is a significant drop in the concentration of the iron-binding protein ferritin. It can be concluded, that reduction of D2-receptors is due to loss of cholinergic and GABA-ergic cell bodies in the striatum or may be a response to iron deficiency. Low serotonergic and high kynurenergic activity may be of pathogenetic importance in the frequently observed cerebral seizures in Rett syndrome.

Amino Acids↗
PubMed1986

Dopamine D2 receptor density remains constant in treated Parkinson's disease.

D2 dopamine receptor densities were measured in postmortem samples of the caudate nucleus and putamen from 36 parkinsonian patients. The relationship between the age of the patient, duration of the disease, and duration of L-dopa therapy versus density of brain D2 dopamine receptors was examined using [3H]spiperone. Receptor density in parkinsonian tissues was constant over the age range of 56 to 90 years, as was the case for control tissues. Density did not change with duration of disease up to 24 years. Treatment with L-dopa did not cause progressive reduction in receptor density. The diminished clinical response in the final stages of Parkinson's disease is not due to receptor dropout, and must depend on other factors.

Age Factors↗
PubMed1986

Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl.

Monoamine oxidase (MAO) type A and type B were measured using kynuramine, 3,4-dihydroxyphenylethylamine (dopamine, DA), and 5-hydroxytryptamine (5-HT, serotonin) in 20 brain areas. The highest activities were found in the striatum (caudate nucleus, putamen, globus pallidus, and substantia nigra), hypothalamus, and c-mammilare. The ratio of DA to 5-HT deamination varied in the different regions, being in favor of DA in the striatum. With kynuramine as the substrate IC50 values of a number of inhibitors indicated that l-deprenyl was far more potent an inhibitor of human brain MAO than clorgyline or harmaline. N-Desmethylpropargylindane hydrochloride (AGN 1135) was also shown to have MAO-B inhibitory selectivity similar to that of l-deprenyl. Brains obtained at autopsy from l-deprenyl-treated Parkinsonian patients showed that, whereas MAO-B was fully inhibited by the therapeutic doses of l-deprenyl, substantial MAO-A activity was still evident. These results are matched by the significant increases of DA noted in caudate nucleus, globus pallidus, putamen, and substantia nigra and the unaltered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the same regions. These data indicate that the therapeutic actions of l-deprenyl may lie in its selective inhibition of MAO-B resulting in increased brain levels of DA formed from L-dihydroxyphenylacetic acid (L-DOPA).

Aged↗
PubMed1986

Biological aspects of depression in Parkinson's disease.

A clinical survey indicates a similar incidence of depression in old age and Parkinson's disease. Divergences, therefore, are apparent, when the biochemical basis of depression is related to the pathobiology of Parkinson's disease (PD) and endogenous depression. However, a common biological concept for endogenous depression and depression in PD is possible by assuming that neurotransmission can operate at various levels of homeostasis. Then depression is the behavioral correlate rather of regional changes that disturb this homeostasis. Therefore, the incidence of depression in old age and PD is similar.

Aged↗
PubMed1986

Hydrogen peroxide enhances the activity of monoamine oxidase type-B but not of type-A: a pilot study.

The effect of hydrogen peroxide on monoamine oxidase (MAO) activity has been determined in homogenates of human brain areas taken postmortem. It could be shown that hydrogen peroxide enhances significantly the activity of MAO-B after short-term incubation (2 min), while no changes have been noted after long-term preincubation (60 min) indicating reversibility of this effect. MAO-A activity was not changed or decreased after preincubation with hydrogen peroxide. Freezing and thawing procedures did not change hydrogen peroxide stimulation of MAO in the caudate nucleus, while MAO-A activity dose dependently decreased. Inhibition of hydrogen peroxide stimulated MAO-B activity in human cortex by (-)deprenyl was found to be of similar potency compared to hydrogen peroxide free estimations. Glutathione, ascorbic acid and mannitol did not block MAO stimulation by hydrogen peroxide, while sodium azide led to a complete inhibition of hydrogen peroxide derived MAO activitation. Interorgan comparison showed increase of MAO-B activity in crude mitochondrial fractions of rat liver after preincubation with hydrogen peroxide, while with rat heart a reduction of MAO activity was detectable. As a conclusion these data indicate a possible role of hydrogen peroxide in the age-dependent increase of MAO-B in platelets and brain. Furthermore, increase of cytotoxic hydrogen peroxide via combined L-dopa therapy cannot be excluded to be of importance in the appearance of adverse reactions after long-term treatment with high doses. To reduce hydrogen peroxide production due to MAO activity, a combined treatment of L-dopa plus a selective MAO inhibitor and eventually additional administration of radical scavengers (ascorbic acid, vitamin E etc.) seems to be indicated.

Adult↗
PubMed1985

[Current biochemical hypotheses of endogenous depression].

In this short introductory review the current important working hypotheses of depression, the noradrenaline and serotonin hypotheses, are described and critically evaluated. Anticholinergic properties, co-modulation of various transmitters by different neuropeptides, great variations in the influence on the "re-uptake" mechanism for noradrenaline and serotonin with no effect by novel antidepressants like iprindole, mianserin and clenbuterol and variability to either stimulate or block receptor systems (alpha 1-, alpha 2-, beta-, serotonin-, dopamine-, adenylate cyclase dependent-, histaminergic receptors and possibly others) might further indicate a complex pathobiochemical background to depression. More recently, a unified hypothesis has been presented on the basis of subsensitivity of the noradrenaline-sensitive adenylate cyclase and/or down regulation of the number of beta-receptors by antidepressants of otherwise different pharmacological properties. Furthermore, another hypothesis, the "brain area specific imbalance of neurotransmitter systems" tries to combine current knowledge of the biochemistry of depressive disorders, the different pharmacological profiles of antidepressants and the divergence of symptomatology in depressed patients. Since antidepressant activity of drugs is dependent on the functional state of pre- and postsynaptic neurotransmission it seems essential to define the basal activity of such systems in vivo and to study the functional change after therapy. Furthermore, phenomena like adaptation and tolerance must be considered in future research in order to get more detailed information about pathobiochemical processes causing depression.

5-Hydroxytryptophan↗