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Biomedical subjects

M Ruberg

Publications and source records attributed to M Ruberg.

At least 91 records · Page 5Linked to original sources
PubMed1985

Adrenergic receptors in frontal cortex in human brain.

The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

Adrenergic alpha-Agonists↗
PubMed1985

Dopaminergic and cholinergic lesions in progressive supranuclear palsy.

In 9 patients with progressive supranuclear palsy and in 27 controls, dopamine and homovanillic acid concentrations, choline acetyltransferase (CAT) activity, and the number of [3H]spiperone and [3H]quinuclidinyl benzilate binding sites were measured post mortem in the striatum (caudate nucleus, putamen, and nucleus accumbens), substantia innominata, and frontal cortex. Dopamine and homovanillic acid concentrations were reduced in the caudate nucleus and putamen but not in the nucleus accumbens or frontal cortex, indicating that the nigrostriatal dopaminergic system is lesioned in patients with progressive supranuclear palsy (as in those with Parkinson's disease) but not the mesocortical and mesolimbic dopaminergic systems, which are lesioned in parkinsonian patients. CAT activity and [3H]spiperone binding decreased in parallel fashion in all the structures. In the striatum, this suggests that the cholinergic neurons, which are target cells of the nigrostriatal system, also degenerate in this disease. This might explain the decrease in the number of dopamine receptors as well as the inefficacy of levodopa or anticholinergic therapy in these patients. The decrease in CAT activity in the substantia innominata and the frontal cortex indicates that the innominatocortical cholinergic system is lesioned in patients with progressive supranuclear palsy and may play a role in the intellectual deterioration observed. This lesion is also found in demented patients with Alzheimer's and Parkinson's diseases.

Aged↗
PubMed1985

Pathophysiology of L-dopa-induced abnormal involuntary movements.

Among the various deficiencies in neurotransmitters and neuropeptides in the brains of patients with Parkinson's disease, the loss of dopamine (DA) is implicated in a major way in the occurrence of L-dopa-induced abnormal involuntary movements (AIMs). Whatever the clinical pattern, they are triggered by drugs which stimulate DA transmission and can be modified by DA agonists and antagonists. They occur when DOPA plasma concentrations, and thus central DA receptor stimulation, reach a critical level. They are observed in patients with severely damaged central DA neurons, but involvement of other neurotransmitter-containing cells cannot be excluded. L-Dopa-induced AIMs have clinical and somatotopic characteristics, which vary from patient to patient. One might speculate that variable damage to DA neurons, associated or not with other neurotransmitter-containing cells in the affected brain structures, causes these differences in AIM patterns. By analogy with behavioral experiments in animals, the hypersensitivity of DA receptors observed in the basal ganglia of parkinsonian patients post mortem might reasonably be considered to mediate L-dopa-induced AIMs. However, the role of various subtypes of DA receptors or of changes in DA metabolism in the cell bodies and dendrites (substantia nigra) or nerve terminals (striatolimbic areas) must also be considered. In brief, the features, topography, and timing of L-dopa-induced AIMs are dependent upon alterations of the functional expression of striatal DA output, which is not yet well understood.

Brain↗
PubMed1985

[Dementia and Parkinson's disease: biochemical and anatomo-clinical correlation].

Intellectual deterioration may be observed in the course of Parkinson's disease. Since it had been reported that central cholinergic systems degenerate in senile dementia and Alzheimer's disease, we measured the activity of choline acetyltransferase (C.A.T.) and the number of muscarinic receptors in various cortical regions of 12 control subjects and 20 patients and compared these biochemical results with clinical and neuropathological data concerning the patients. Thirteen of the parkinsonian patients showed signs of intellectual decline (moderate in 8, severe in 5) and neuropathological examination of the cortex revealed in 10 cases large number of Alzheimer type senile changes extending beyond the hippocampus. C.A.T. activity was decreased in the cerebral cortex in every patient. The decrease was greater in intellectually deteriorated patients and in the group with numerous senile changes in the cortex. The number of muscarinic receptors was increased in patients that had been treated with anticholinergic drugs until they died, but also in those who had not received these drugs, suggesting and underlying denervation hypersensitivity. In the caudate nucleus, however, neither C.A.T. activity nor muscarinic receptor number was altered, indicating that the cortical cholinergic lesion was specific. Although in most cases dementia in Parkinson's disease was of the Alzheimer type, the case of a demented parkinsonian patient in whom cortical C.A.T. activity was severely decreased, in spite of the absence of cortical histopathological evidence characteristic of Alzheimer's disease, suggests that a parkinsonian dementia different from the Alzheimer type also exists. In Parkinson's disease as in Alzheimer's disease the decrease in C.A.T. activity in the cerebral cortex results from degeneration of the cholinergic neurones in the nucleus of Meynert which projects to the cortex. Although the severity of intellectual deterioration seems in relationship with the extent of degeneration, this could already begin before intellectual impairment is apparent.

Aged↗
PubMed1984

Adrenergic receptors in Parkinson's disease.

Alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors were measured in the pre-frontal cortex of parkinsonian patients post-mortem. The number of beta 2 receptors was the same in control and parkinsonian subjects. alpha 1 and beta 1 receptors increased in number, particularly in demented parkinsonian patients, while alpha 2 receptors decreased. The affinity constants were unchanged. The modifications seem to be related to lesion of the noradrenergic pathway from the locus coeruleus to the cortex. The relationship between this lesion and the symptoms of dementia and depression in parkinsonian patients is discussed.

Clonidine↗
PubMed1984

[3H]spiperone binding in the nigrostriatal system in human brain.

The characteristics of [3H]spiperone binding in human brain were compared in three areas of the nigrostriatal pathway: areas containing the nerve terminals (caudate nucleus, putamen and pallidum); the area containing the cell bodies (substantia nigra pars compacta); the area containing the dendrites (pars reticulata). The affinity constants were calculated from saturation binding curves and from the kinetics of association and dissociation. The pharmacological profiles of the receptors was also established by displacement studies. The affinity constants and pharmacological profiles were similar in the striatum and the substantia nigra, although the latter contained a much smaller number of sites. In the substantia nigra, however, curved Scatchard plots were obtained, indicating that a second lower affinity site binding [3H]spiperone was also present. A considerable proportion (50%) of [3H]spiperone binding to nigral membranes could be displaced by the serotonin antagonist cinanserine , compared to the striatum (20%). The effect of post-mortem conditions on binding levels was studied in the rat. A loss of 20% occurred during the first hours after death, but was stable by 6 h until at least 24 h.

Aged↗
PubMed1984

[3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy.

The density of D2-type dopamine receptors, measured by the binding of [3H]spiperone was normal in the substantia nigra, caudate nucleus and nucleus accumbens of Parkinsonian subjects and above control levels in the putamen, in spite of massive lesions of the dopaminergic neurons. Dopamine levels were reduced in the putamen, caudate nucleus, and nucleus accumbens by 97, 85 and 68%, respectively and by 78 and 93% in the pars compacta and pars reticulata of the substantia nigra. HVA levels were much less affected suggesting that increased activity of the remaining dopaminergic neurons compensated to some extent for the lesions. Neuroleptic treatment and the presence of dementia in the Parkinsonian subjects affected [3H]spiperone binding and dopamine concentrations. Dopamine and HVA levels in the striatum of subjects with supranuclear palsy indicate that the nigrostriatal system was lesioned to the same degree in this disease as in idiopathic Parkinsonism, but spiperone binding was reduced by half in all the structures studies.

Aged↗
PubMed1984

Biochemistry of the hypothalamus in Parkinson's disease.

We assayed the content of neurotransmitters (or their synthesizing enzymes) and neuropeptides in the hypothalamus of control and parkinsonian brains post mortem. Only dopamine concentrations were lower than normal in Parkinson's disease, suggesting that deficiency in hypothalamic dopamine transmission may play a role in the autonomic and endocrine abnormalities of this disorder.

Aged↗
PubMed1983

A subcortico-cortical cholinergic system is affected in Parkinson's disease.

CAT activity was decreased in the frontal cortex and the substantia innominata of parkinsonian subjects, post-mortem. The decrease was greater in the frontal cortex of parkinsonians with dementia. The density of muscarinic cholinergic receptors increased in the cortex. This increase was inversely correlated with tremor. The effects on these parameters of both neuronal degeneration and anticholinergic therapy are discussed.

Aged↗
PubMed1983

Somatostatin and dementia in Parkinson's disease.

The concentrations of somatostatin in the cortex, hippocampus and caudate nucleus of subjects with Parkinson's disease were determined by radioimmunoassay. Somatostatin levels in the frontal cortex were significantly reduced in Parkinsonian subjects who were slightly or severely demented compared to controls and to non-demented Parkinsonians. Significant reductions were also observed in the hippocampus and entorhinal cortex of severely demented subjects.

Aged↗
PubMed1983

[3H]imipramine binding in subcellular fractions of rat cerebral cortex after chemical lesion of serotonergic neurons.

The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.

5,7-Dihydroxytryptamine↗
PubMed1982

Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia.

[3H]Quinuclidinylbenzilate ([3H]QNB) binding and choline acetyltransferase (CAT) activity were studied in post-mortem brains from control and Parkinsonian subjects. CAT levels were reduced in the cortex and hippocampus of Parkinsonians. The apparent affinity of [3H]QNB for the muscarinic receptor was higher in both the caudate nucleus and the frontal cortex. Receptor density increased only in the frontal cortex. These changes are discussed in relation to dementia and mental disturbances following anticholinergic treatment frequently observed in Parkinson's disease.

Aged↗
PubMed1982

Confusion, dementia and anticholinergics in Parkinson's disease.

Among a population of 75 hospitalised Parkinsonian subjects, confusional states were observed in 46% of demented patients not receiving anticholinergic drugs and in 93% of demented patients under anticholinergic therapy. The sensitivity of demented Parkinsonians to anticholinergic drugs can be attributed to a cholinergic deficiency which has been detected in the cortex and hippocampus of Parkinsonian patients post-mortem. The observations suggest that anticholinergic medication should be avoided in Parkinsonians with intellectual impairment.

Cognition Disorders↗