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M Ruberg

Publications and source records attributed to M Ruberg.

At least 73 records · Page 4Linked to original sources
PubMed1992

Decreased choline acetyltransferase mRNA expression in the nucleus basalis of Meynert in Alzheimer disease: an in situ hybridization study.

The subnormal choline acetyltransferase (ChoAcTase) activity in the cerebral cortex of patients with Alzheimer disease (AD) is thought to originate from the loss of cholinergic neurons in the nucleus basalis of Meynert (nbM). To examine possible changes in the functional activity of the remaining cholinergic neurons in the nbM of patients with AD, the level of expression of ChoAcTase mRNA was evaluated. A procedure for double-labeling cholinergic neurons to detect ChoAcTase mRNA and the corresponding protein in the same cell was developed, taking advantage of an anti-ChoAcTase antibody and the recently isolated cDNA complementary to a sequence of the human ChoAcTase mRNA. In the study of three controls and four patients with AD, the presence of both ChoAcTase mRNA and protein was observed in the same large neurons in both nbM and putamen. Specificity of in situ hybridization was further supported by the absence of neuronal staining with a sense probe. In AD patients a subnormal level of expression of ChoAcTase mRNA per cholinergic cell was detected in the nbM but not in the putamen. Our data support the hypothesis that expression of ChoAcTase mRNA might be down-regulated in the surviving cholinergic neurons in the nbM of patients with AD, raising the possibility of functional restoration by stimulating ChoAcTase synthesis.

Alzheimer Disease↗
PubMed1992

Does loss of nerve growth factor receptors precede loss of cholinergic neurons in Alzheimer's disease? An autoradiographic study in the human striatum and basal forebrain.

The mechanism by which cholinergic neurons degenerate in Alzheimer's disease is not known. Some of these neurons depend, however, on trophic support from NGF via a membrane receptor. We have analyzed the state of these receptors by autoradiography, with 125I-NGF as the ligand, in the caudate nucleus, putamen, ventral striatum, nucleus basalis of Meynert, and nucleus tegmenti pedunculopontinus of six patients with Alzheimer's disease and five controls, matched for age and postmortem delay. The binding characteristics were similar in the striatum (including caudate nucleus, putamen, and ventral striatum) and basal forebrain of control subjects and patients with Alzheimer's disease (Kd = 2.5-4 x 10(-11) M). In control brains, high levels of 125I-NGF binding were observed in the basal forebrain and striatum (0.32-0.49 fmol/mg tissue equivalent), but no specific binding was detected in the nucleus tegmenti pedunculopontinus. NGF binding sites were distributed heterogeneously in the striatum with patches of low density, corresponding to AChE-poor striosomes, surrounded by a matrix in which receptor density was significantly greater. In Alzheimer's disease, the density of NGF receptors was markedly decreased in the caudate nucleus, putamen, ventral striatum, and nucleus basalis of Meynert. In contrast, AChE staining decreased less in the nucleus basalis of Meynert in all Alzheimer's disease patients, and in the ventral striatum of those most severely affected. These results indicate that if NGF receptors are located on cholinergic neurons, receptor loss and the consequent decrease in trophic support may precede cell degeneration in Alzheimer's disease. The relationship between the loss of these receptors and the pathogenesis of the disease remains to be determined.

Acetylcholinesterase↗
PubMed1990

Tyrosine hydroxylase-like immunoreactivity in senile plaques is not related to the density of tyrosine hydroxylase-positive fibers in patients with Alzheimer's disease.

The numbers of silver-stained senile plaques and plaques containing tyrosine hydroxylase (TH)-like immunoreactivity were counted in the neocortex, amygdala and hippocampus of control subjects and patients with Alzheimer's disease, and compared with the density of TH-positive nerve fibers. The number of silver-stained senile plaques was lowest in the hippocampus and highest in the amygdala, and increased in all three structures in relation to the degree of dementia in the patients. A small proportion of plaques in the hippocampus of the most demented subjects and a large proportion of plaques in the amygdala were TH-positive. No TH-like immunoreactivity was found in plaques in the neocortex, although this structure contained almost as many silver-stained senile plaques and was as densely innervated by TH-positive fibers as the amygdala. The number of plaques containing TH-like immunoreactivity was, therefore, not proportional to the innervation of the structures by TH-positive fibers, nor to the total number of plaques in the structure, suggesting that the dissociation between the proportion of TH-positive plaques in the amygdala and neocortex may be due to differences in the populations of TH-positive fibers innervating the structures.

Aged↗
PubMed1990

Choline acetyltransferase activity and [3H]vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions.

[3H]Vesamicol binding was characterized in human brain post mortem. The number of binding sites was then determined in parallel with choline acetyltransferase activity in the temporal cortex of patients with Alzheimer's disease, demented and non-demented patients with Parkinson's disease, and in the cerebral cortex of rats with quisqualic acid lesions of the nucleus basalis magnocellularis. Whereas choline acetyltransferase activity decreased in patients with Alzheimer's or Parkinson's disease indicating loss of cholinergic innervation, the number of binding sites for [3H]vesamicol was the same as or higher than in controls. Similar results were obtained with the lesioned rats. It is suggested that the increase in binding sites may reflect compensatory regulation of the spared neurons at the level of the synaptic vesicle.

Aged↗
PubMed1990

Decreased ferritin levels in brain in Parkinson's disease.

Ferritin levels were measured in postmortem brain tissue from patients dying with Parkinson's disease [treated with L-3,4-dihydroxyphenylalanine (L-DOPA)] and from control patients. Ferritin levels were decreased in the substantia nigra, caudate-putamen, globus pallidus, cerebral cortex, and cerebellum when compared with age-matched control tissues. However, in CSF from L-DOPA-treated patients and in serum from L-DOPA-treated and untreated parkinsonian patients, ferritin levels were normal. Previous studies have suggested an increased total iron content in substantia nigra of parkinsonian brain. The failure of substantia nigra ferritin formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease. The reason for decreased ferritin levels throughout the parkinsonian brain is not clear but does not seem to reflect a general system deficit in ferritin.

Brain Chemistry↗
PubMed1989

Distribution of monoaminergic, cholinergic, and GABAergic markers in the human cerebral cortex.

Mapping of a number of biochemical markers for noradrenergic, dopaminergic, serotoninergic, cholinergic and GABAergic systems was undertaken in 93 samples removed from the human cerebral cortex. The right hemisphere of brains from two subjects with no known history of neurological and psychiatric diseases was examined. Neurotransmitter markers were present in all cortical samples analysed, suggesting a widespread distribution of the corresponding neurons throughout the cerebral cortex. Each marker distributed heterogeneously in a distinct pattern. Noradrenaline concentrations were highest in the frontoparietal region and lowest in prefrontal and occipital areas. Markers for dopaminergic neurons (dopamine levels, dopamine/noradrenaline ratio and homovanillic acid levels) seemed denser in the prefrontal and temporal regions. 5-Hydroxyindolacetic acid levels were particularly high in the occipital area and decreased along the caudorostral axis. Choline acetyltransferase activity was highest in temporal and frontal lobes, at variance with muscarinic receptor distribution, which was highest in occipital cortex. Glutamate decarboxylase activity, an index of GABAergic innervation, did not vary markedly among the different areas of the cerebral cortex. The different biochemical markers investigated were detected in all cerebral cortical regions; their distribution was not homogeneous. A mismatch was observed between the distribution of cholinergic neuronal systems and receptors.

Aged↗
PubMed1989

Choline acetyltransferase-like immunoreactivity in the hippocampal formation of control subjects and patients with Alzheimer's disease.

A qualitative and quantitative immunohistochemical study of cholinergic systems in the human hippocampal formation was performed with an antibody against choline acetyltransferase. Four control subjects and six patients with Alzheimer's disease, matched for age and post-mortem delay, were examined. Immunoreactive nerve fibres and terminals were visualized, but no cholinergic cell bodies were seen. The distribution of the fibres and terminals suggests that a major afferent cholinergic pathway enters the hippocampus dorsally via the fimbria-fornix, a minor input entering from the temporal lobe along the alvear path. The cholinergic innervation suffers some degenerative change in normal aged subjects, but decreases considerably in density in patients with Alzheimer's disease. The extent of the decrease differs somewhat among the subregions of the hippocampus, but is homogeneously distributed within each subregion, and throughout the rostrocaudal extent of the structure. Compensatory sprouting in reaction to denervation was not detected.

Aged↗
PubMed1989

Selective loss of cholinergic neurons in the ventral striatum of patients with Alzheimer disease.

Cholinergic neurons were studied by immunohistochemistry with an antiserum against human choline acetyltransferase in the caudate nucleus, putamen, and ventral striatum (including the nucleus accumbens) of three patients with Alzheimer disease and three control subjects. Immunoreactive cell bodies were mapped and counted. In the ventral striatum of patients with Alzheimer disease, a 60% decrease in the number of cholinergic neurons was observed, whereas in the caudate nucleus and putamen values for control subjects and patients were similar. To determine whether all neurons in the ventral striatum were affected, neuropeptide Y-containing neurons were also immunostained, mapped, and counted. The number of these neurons was the same in control subjects and patients with Alzheimer disease, indicating that neuronal loss is not generalized in the ventral striatum and may be specific to the cholinergic population.

Acetylcholinesterase↗
PubMed1988

Characterization of two antigens in parkinsonian Lewy bodies.

Two antigens, G7 and G9, which are labelled by monoclonal antibodies in Lewy bodies in brains from patients with Parkinson's disease, were characterized by two-dimensional electrophoresis, followed by electroblotting, in order to explore their possible relationship with neuronal degeneration in this disease. The G7 antigen was found in the substantia nigra of subjects with Parkinson's disease and progressive supranuclear palsy, as well as in normal subjects. It was also found in the dopaminergic nucleus paranigralis and the locus coeruleus. The G9 antigen was found in the substantia nigra and locus coeruleus, but also in the caudate nucleus, terminal region of the nigrostriatal dopaminergic neurons, and in the cortex and cerebellum, terminal regions of the noradrenergic neurons in the locus coeruleus. The identity of the antigens remains unknown. They do not correspond to tyrosine hydroxylase or neurofilaments previously detected in Lewy bodies, or to other cytoskeletal proteins. Nor are they related to the presence of neuromelanin in the cells that degenerate in Parkinson's disease. The proteins, or at least the epitopes labelled by the antibodies, are found in normal brain, suggesting that these proteins do not play a causal role in the formation of the Lewy bodies in degenerating neurons in Parkinson's disease. The G7 antigen is absent from the cholinergic substantia innominata, where Lewy bodies are also found, indicating that these antigens are not essential for the formation of the corpuscle.

Antigens↗
PubMed1988

D1 and D2-type dopamine receptors in patients with Parkinson's disease and progressive supranuclear palsy.

The densities of D1- and D2-type dopamine receptors were measured with [3H]SCH23390 and [3H]spiperone, in the caudate nucleus and putamen of a large series of patients with Parkinson's disease or progressive supranuclear palsy, in relation to markers of dopaminergic and cholinergic innervation of the striatum ([3H]dihydrotetrabenazine binding and choline acetyltransferase activity). Correlations were sought between these parameters and clinical characteristics of the patients (abnormal involuntary movements, dementia, confusional syndrome or treatment). In Parkinson's disease, the densities of both types of receptors were unchanged, whereas in PSP, the density of D2, but not D1-type dopamine receptors, was decreased in the caudate nucleus and the putamen. No correlations between the biochemical and clinical data were found.

Adenylyl Cyclases↗
PubMed1987

Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were assayed in the cerebrospinal fluid (CSF) of subjects with neurodegenerative diseases (dementing and non-dementing, with and without known cholinergic lesions), to determine whether CSF AChE is a valid marker of central cholinergic activity. The relative proportions of the different forms of each enzyme and of AChE to BChE were similar in CSF and brain. AChE decreased in Huntington's chorea (degeneration of striatal cholinergic interneurons) but also in multiple sclerosis (not known to affect cholinergic systems). BChE paralleled AChE, although the enzymes were dissociated in some patients. It is concluded that CSF AChE activity may globally reflect brain AChE, but pathology-induced changes may not be directly reflected.

Acetylcholinesterase↗
PubMed1986

Acetylcholinesterase and butyrylcholinesterase in frontal cortex and cerebrospinal fluid of demented and non-demented patients with Parkinson's disease.

The molecular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were studied in frontal cortex (grey and white matter), postmortem, and in cerebrospinal fluid (CSF) of demented patients with Parkinson's disease compared to controls and non-demented parkinsonians. In the frontal cortex, AChE activity decreased significantly in both demented and non-demented parkinsonian subjects compared to controls; the 10S form of the enzyme was significantly lower in demented parkinsonians than in the non-demented subjects. The decrease in AChE activity was correlated with a decrease in choline acetyltransferase activity thought to reflect lesion of cholinergic neurones in the substantia innominata which innervate the cerebral cortex. BChE activity decreased only in the non-demented parkinsonians; in the demented subjects, BChE activity was at control levels. Similar results were obtained with grey and white matter, although absolute levels of the two enzymes were different in the two types of tissue, suggesting that the enzymes were affected in the cholinergic neurones before transport to cortical nerve terminals. No decreases in AChE or BChE activity were observed in the CSF of the patients studied. On the contrary, AChE and BChE levels were significantly higher in demented parkinsonian patients compared to the non-demented subjects.

Acetylcholinesterase↗
PubMed1985

Monoclonal antibodies raised against Lewy bodies in brains from subjects with Parkinson's disease.

Monoclonal antibodies which immunocytochemically label Lewy bodies on sections of substantia nigra from subjects with Parkinson's disease were produced by immunization of mice with substantia nigra and locus coeruleus containing Lewy bodies from parkinsonian subjects post-mortem. Tests of specificity indicate that the antibodies do not recognize the same antigen. One of the antibodies (G7) immunocytochemically labels only Lewy bodies, the other (G9) also faintly labels the cell bodies of nigral dopaminergic neurons and cerebellar Purkinje cells in both normal and parkinsonian brains. Absorption experiments show, however, that the G7 antigen is present in normal substantia nigra and the G9 antigen in normal substantia nigra and Purkinje cells. Neither of the antibodies seems to be directed against neurofilament protein. Immunoblots after two-directional electrophoresis indicate that antibody G7 labels a protein with an iso-electric point around 5.6 and a mol. wt. of approximately 40 kdalton, whereas the protein labeled by antibody G9 has an iso-electric point of near 8 and a mol. wt. above 70 kdalton.

Antibodies, Monoclonal↗