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Biomedical subjects

L Volicer

Publications and source records attributed to L Volicer.

At least 73 records · Page 4Linked to original sources
PubMed1991

Laminar alterations in gamma-aminobutyric acidA, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer's disease.

The laminar distribution of binding to a number of postsynaptic neurotransmitter receptors was assessed autoradiographically in postmortem samples of area 23a in posterior cingulate cortex from 13 Alzheimer and nine age-matched control cases. Specific binding in all Alzheimer cases was compared to that in control cases, and the following alterations were observed: reduced muscimol binding in most layers; no changes in pirenzepine binding; and elevated cyanopindolol binding in layers Ic, IIIc, and IV. The Alzheimer cases were classified further on the basis of neuronal degeneration: class 1, no neuron loss; class 2, greatest losses in layer II or III; class 3, greatest losses in layer IV; and class 4, greatest losses in layer V or VI. This classification uncovered further alterations in ligand binding patterns. First, muscimol binding was reduced in layers II and III only in class 2 cases and in layers V and VI only in class 4 cases. Second, pirenzepine binding was reduced in layers Ic, IIIa-b, and VI of class 1 cases and layers Va and VI of class 4 cases. In spite of neuron degeneration in classes 2 and 3, there was no change in pirenzepine binding in these classes. Third, elevated cyanopindolol binding occurred in classes 3 and 4, whereas classes 1 and 2 had normal levels of binding. These results suggest that cases of Alzheimer's disease express heterogeneities in neocortical pathology which are reflected in the laminar patterns of binding to postsynaptic receptors. Reductions in muscimol binding to the gamma-aminobutyric acidA receptor had the closest relationship with neuron degeneration, whereas pirenzepine binding appeared to reflect a compensation in muscarinic receptors for changes in neuron densities.

Adrenergic beta-Antagonists↗
PubMed1991

Modification of brain guanine nucleotide-binding regulatory proteins by tryptamine-4,5-dione, a neurotoxic derivative of serotonin.

We have recently characterized a novel oxidation product of serotonin (5-hydroxytryptamine, 5-HT), tryptamine-4,5-dione, which increases 5-HT efflux from striatum and hippocampus and causes selective neuronal death. Exposure of striatal synaptosomes or the major brain guanine nucleotide-binding regulatory proteins Gi and Go to [3H]tryptamine-4,5-dione resulted in the radiolabeling of a major band with an apparent molecular mass equivalent to that of the alpha subunits of Gi and Go (approximately 40,000). The binding of [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTP-gamma-S) to Gi and Go and pertussis toxin-catalyzed [32P]ADP-ribosylation of the G protein alpha subunits were both inhibited in a dose-dependent manner by tryptamine-4,5-dione. Thus, neurotoxins such as tryptamine-4,5-dione may exert their effects through specific interactions with G proteins.

Adenosine Diphosphate Ribose↗
PubMed1991

Circadian locomotor activity rhythms in Alzheimer's disease.

Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment.

Aged↗
PubMed1990

Effect of antibiotic treatment on outcome of fevers in institutionalized Alzheimer patients.

Fever episodes in 104 institutionalized patients with Alzheimer's disease were prospectively evaluated to determine the impact of antibiotic treatment on fever outcomes. During the 34-month observation period, 75 patients developed 172 episodes of fever and 29 patients had no fevers. Patients who developed fevers had more advanced disease than patients who did not. Patients who received diagnostic workup of all fevers and treatment with antibiotics (Antibiotic Group) were compared with patients who received comfort measures only (Palliative Group). The incidence of fever was similar in the Antibiotic and Palliative groups. Survival analysis revealed that, for the more severely affected patients, there was no difference in survival between the groups. Among less severely affected patients, survival was higher for the Antibiotic than the Palliative Group. These results suggest that treatment of fever with antibiotics does not alter the outcome of fever in patients with advanced Alzheimer's disease.

Age Factors↗
PubMed1990

Neuropsychological profile linked to low dopamine: in Alzheimer's disease, major depression, and Parkinson's disease.

A distinct pattern of neuropsychological deficits was associated with low homovanillic acid (HVA) in the cerebrospinal fluid of 21 patients with: Alzheimer's disease (9), Parkinson's disease (8) and major depressive disorders (4). Regardless of clinical diagnosis, patients with low HVA were slower on a test of efficiency of processing timed information, and showed greater benefit from semantic structure on a verbal fluency task than patients with high HVA. However, low HVA subjects were not significantly impaired on confrontation naming (Boston Naming Test). Across three diagnostic groups, patients with lower HVA also tended to have more extrapyramidal motor signs and were significantly more depressed. These results demonstrate a significant relationship between specific neuro-behavioural deficits and dopaminergic activity which cuts across traditional diagnostic categories.

Aged↗
PubMed1990

Cellular localization of serotonin 1A, 1B and uptake sites in cingulate cortex of the rat.

Experimental lesions followed by binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), [125I]cyanopindolol and [3H] paroxetine to cryostat sections and coverslip autoradiography were used to localize 5-HT1A, 5-HT1B and 5-HT uptake sites in rat posterior cingulate cortex. Ablations included: 1) undercutting for removal of all afferent axons; 2) destruction of the raphe nuclei; 3) cortical ibotenic acid injections for removal of neurons and 4) anterior thalamic and caudate nuclei injections of the immunotoxin OX7-saporin which destroys single classes of cortical projection neurons by retrograde axonal transport. Peak paroxetine binding was in layer Ia with low binding in layer Va and moderate amounts in other layers. Undercut lesions reduced binding only in layer Ia by 35%. Major loses were observed after raphe ablations with decreases of 40 to 72% across all layers. Cortical ibotenic acid injections did not alter paroxetine binding. Peak cyanopindolol binding was in layers Ia to Ic. Undercutting decreased binding significantly in layers Ia, Ib, III and IV, whereas after raphe lesions binding was decreased by 34 to 58% in layers Ia to IV. 5,7-Dihydroxytryptamine injection increased binding by 10 to 40% in layers Ib, II, III and IV. Cortical ibotenic acid injections reduced grain density in all layers with a range of 28 to 47%. Peak 8-OH-DPAT binding was in layer Vb. No change was observed after undercut lesions, whereas after cortical ibotenic acid injection, binding reductions of 44 to 75% were observed throughout all nine sublaminae. Thalamic OX7-saporin injections destroyed almost all layer VI neurons, which resulted in a 45% decrease in layer VI 8-OH-DPAT binding.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Neurotoxic effects of partially oxidized serotonin: tryptamine-4,5-dione.

Neurotoxicity of tryptamine-4,5-dione (4,5-DKT), a partially oxidized form of serotonin, was assessed after microinjection into the lateral ventricle, hippocampus, or cingulate cortex of rats followed by Fink-Heimer staining for axon terminal degeneration. Intracerebroventricular injections of 4,5-DKT resulted in terminal degeneration which was most dense in layers I and III of insular cortex, layer I of cingulate cortex, and the molecular layer of the dentate gyrus. Argyrophilic and probably degenerating neurons were most frequently subjacent to the granule cell layer of the dentate gyrus, layers II, III, and IV of entorhinal cortex, and throughout the insula. Injections of 5-20 micrograms of 4,5-DKT directly into the hippocampus indicated that toxicity was dose-dependent. These injections produced axon terminal degeneration and neuronal argyrophilia in sectors CA1 and CA3 and in the dentate gyrus. Argyrophilic neurons were also observed in layers II, III, and IV of ipsi- and contralateral entorhinal cortices. Injections into anterior and posterior cingulate cortices produced degeneration in the caudate and anterior thalamic nuclei, and contralateral cortex. These results indicate that 4,5-DKT is a novel indole neurotoxin which exhibits a striking propensity for medial limbic system structures including some of those affected in dementia of the Alzheimer type.

Animals↗
PubMed1989

Brain gangliosides in dementia of the Alzheimer type.

Gangliosides GM1, GD1a, GD1b, and GT1b were measured in nine brain regions of five patients, clinically and neuropathologically diagnosed as having dementia of the Alzheimer type (DAT), and of three control patients. Analysis of variance revealed that mean concentrations of all gangliosides analyzed were significantly lower in DAT than in control brains. The areas affected in DAT included the nucleus basalis, and entorhinal, posterior cingulate, visual, and prefrontal cortices. A significant interaction between ganglioside type and brain area indicated unequal ganglioside concentrations. Individual gangliosides had significantly different concentrations in the hippocampal, entorhinal, posterior cingulate, visual, and prefrontal cortices. Analysis of ratios of "a"-ganglioside (GM1 and GD1a) and "b"-ganglioside (GD1b and GT1b) subtypes indicated that DAT preferentially affected "b"-gangliosides. Ganglioside concentrations in nucleus basalis did not correlate with age at disease onset, age at death, or postmortem interval. Changes in gangliosides, observed in this study, were not correlated with classic DAT neuropathology.

Aged↗
PubMed1989

Increased serotonin efflux by a partially oxidized serotonin: tryptamine-4,5-dione.

A partially oxidized serotonin (5-HT) was synthesized electrochemically from 5-HT in an acidic solution. This compound was characterized by its chromatographic and electrochemical properties and identified by mass spectroscopy and NMR as tryptamine-4,5-dione (4,5-DKT). In in vitro superfusion experiments, 10(-5)M 4,5-DKT significantly increased the basal 5-HT efflux from both rat hippocampal and striatal fragments. In contrast, 10(-5) M 4,5-DKT did not change the release of dopamine or its metabolite, 3,4-dihydroxyphenylacetic acid from striatal fragments. Continuous perfusion of 4,5-DKT did not modify the effect of KCl on either 5-HT or dopamine release from both brain areas. In in vitro incubation experiments, 10(-8) to 10(-5) M 4,5-DKT evoked 5-HT efflux from rat hippocampus in a dose-dependent fashion. When 10(-4) and 10(-5) M fluoxetine was incubated with 10(-6) M 4,5-DKT, it partially blocked 4,5-DKT-induced 5-HT release. Pargyline, at 10(-5) M inhibited significantly the 5-hydroxyin-doleacetic acid efflux, but did not modify the 4,5-DKT-stimulated 5-HT release. Incubation of 4,5-DKT with glutathione (GSH) and mercaptoethanol indicated that 4,5-DKT binds to sulfhydryl groups. An evidence of GSH-4,5-DKT conjugate was also observed after incubation of 4,5-DKT with a brain homogenate. The interaction of 4,5-DKT with GSH or mercaptoethanol was blocked effectively with N-ethylmaleimide. It is possible that sulfhydryl groups are involved in the mechanism of 4,5-DKT action on 5-HT release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Neurotoxic properties of a serotonin oxidation product: possible role in Alzheimer's disease.

Properties of a partially oxidized form of serotonin (5-HT), 4,5-diketotryptamine (4,5-DKT), synthesized by electrochemical oxidation of 5-HT, were investigated. Administration of 4,5-DKT into the lateral ventricles (i.c.v.) of rats resulted in cell death and terminal degeneration in entorhinal, insular, and posterior cingulate cortices, and in the CA1, CA3 and dentate gyrus sectors of hippocampus. Furthermore, i.c.v. administration of 4,5-DKT resulted in a significant depletion of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in prefrontal cortex, striatum and hippocampus. 4,5-DKT injection into cingulate and hippocampal cortices resulted in cell death and terminal degeneration in these structures. In brain fragment perfusion and incubation experiments, 4,5-DKT increased dose dependently 5-HT efflux from rat hippocampus and striatum. The efflux of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid from striatum was unaffected. In hippocampal preparations, fluoxetine decreased 4,5-DKT-stimulated efflux of 5-HT by 24%, and pargyline did not affect it. In vitro, 4,5-DKT bound covalently to nucleophilic -SH groups in glutathione and mercaptoethanol and the binding was blocked by N-ethyl-maleimide. 4,5-DKT bound selectively to purified guanine nucleotide binding proteins, and inhibited pertussis toxin-catalyzed ribosylation at 1nM-1 microM concentrations. Analysis of cerebrospinal fluid (CSF) by a 16-channel high pressure liquid chromatography with coulometric detection did not confirm presence of 4,5-DKT in Alzheimer CSF, but detected several peaks, significantly different in control and Alzheimer CSF, which were caused by unknown compounds.

Alzheimer Disease↗
PubMed1987

Acute hepatic damage in rats impairs metharbital metabolism.

Metharbital metabolism was impaired in rats after acute hepatic damage induced by carbon tetrachloride. Compared to control rats, hepatic damage prolonged the metharbital sleeping time and reduced the slopes of log metharbital plasma concentration-time curves. Renal contributions to metharbital elimination from plasma were negligible since only about 6% of the metharbital administered was eliminated unchanged in urine. In rats with hepatic damage, metharbital clearance from plasma and elimination of its demethylated metabolite, barbital, in urine decreased with increasing severity of damage. These results indicate that the kinetics of both metharbital and its metabolite reflect sensitively hepatic drug-metabolizing capacity. Measuring urinary elimination of barbital, following metharbital administration, may serve as a convenient laboratory test to evaluate the hepatic drug-metabolizing capacity.

Acute Disease↗
PubMed1986

Systematic regional differences in the cholinergic innervation of the primate cerebral cortex: distribution of enzyme activities and some behavioral implications.

Choline acetyltransferase and acetylcholinesterase enzymatic activities were measured in 33 cytoarchitectonic subregions of the cerebral cortex in two rhesus monkeys. As expected, the hippocampus and amygdala were rich in these enzymes. In addition, the paralimbic (mesocortical) regions of the brain (e.g., parahippocampal, insular, caudal orbitofrontal, and temporopolar areas) also contained high levels of both enzymes. In contrast, the concentration of these cholinergic markers was the lowest within all frontal and temporoparietal association areas. As a group, the primary sensory and motor regions contained an intermediate level of choline acetyltransferase activity. Both cholinergic markers also showed a gradual increase from the isocortical toward the more primitive periallocortical subsectors of paralimbic areas. These anatomical patterns have potential implications for the role of cholinergic pathways in the memory process and in the pathogenesis of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1986

Distribution of the molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type.

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane-bound form (G4) and a monomeric soluble form (G1) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages. The results demonstrate an overall loss of protein and enzyme activity in all areas of the DAT brains studied and a selective loss of the G4 form of AChE in Brodmann areas 9, 10, 11, 21, 22, and 40, and the amygdala. There was no change in the G4/G1 ratio in areas 17 and 20, in the hippocampus, or in the cerebellum. There was a high regional correlation of the G4/G1 ratios with published values for choline acetyltransferase activity but lower correlation with total AChE activity. We propose that there is a predominant loss of the G4 form of AChE in DAT and that this loss is correlated with the degeneration of presynaptic elements.

Acetylcholinesterase↗
PubMed1986

Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study.

Mean levels of the two hydrolases angiotensin-converting enzyme (ACE) and acetylcholinesterase (AChE), the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and total protein concentration were examined in cerebrospinal fluid (CSF) samples from a group of patients with dementia of the Alzheimer's type, a group of comparably demented patients with Parkinson's disease, and a neurologically healthy elderly control group. Both pathological groups exhibited a significant decrease in the mean levels of ACE activity and DOPAC per milliliter and were distinguishable from one another based on mean CSH HVA levels. Unlike the Parkinson's disease group, whose mean concentration of HVA was lower than, but not significantly different from that of the control group, the mean HVA concentration of the Alzheimer's disease group was significantly elevated. In contrast, comparisons of the mean CSF AChE activity (expressed per milliliter or per milligram of protein) and CSF total protein concentration did not reveal significant differences for any of the groups. Independent of CSF protein concentration, ACE activity per milliliter exhibited a positive correlation with AChE activity per milliliter within the control and Parkinson's disease groups, whereas a statistically significant correlation for these CSF hydrolases was not observed within the Alzheimer's disease group. Thus, the CSF profiles for patients with mild dementias associated with Alzheimer's or Parkinson's disease differed by at least two neurochemical criteria. Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects (n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups.

3,4-Dihydroxyphenylacetic Acid↗