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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 451 records · Page 25Linked to original sources
PubMed1985

Elevated density of [3H]imipramine binding in aged human brain.

Aging was associated with an increase in the density of specific binding sites for [3H]imipramine in postmortem specimens of human hypothalamus, frontal cortex, and parietal cortex. In general, [3H]imipramine binding was not affected by factors considered difficult to control in postmortem studies, i.e., time from death to autopsy and cause of death. The in vitro regulation of [3H]imipramine binding by sodium was impaired with age in hypothalamic homogenates. In vitro regulation of [3H]imipramine binding by chloride was intact. Determination of the concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid in hypothalamus and frontal cortex indicated no apparent age-related changes in indole metabolism. The age-related increase in brain [3H]imipramine binding and impairment in the in vitro regulation of binding by ions are similar to changes observed previously in aged mouse brain. The increase in brain antidepressant binding sites is discussed in relationship to other indices of brain serotonergic function in aging and to the relationship of [3H]imipramine binding and depression.

Adolescent↗
PubMed1985

"Specific" binding of [3H]imipramine to protease-sensitive and protease-resistant sites.

A number of 5-hydroxytryptamine (5-HT) uptake inhibitors have been shown to displace the binding of [3H]imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of [3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 microM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10 microM desipramine. The protease-sensitive [3H]imipramine binding sites were found to be saturable, high-affinity binding sites with a KD of 8 nM. The number of these sites varied between brain regions and was positively correlated with the regional distribution of [14C]5-HT but not [3H]noradrenaline uptake. This was not the case however for the protease-resistant but desipramine-displaceable binding sites. Since most previous [3H]imipramine binding studies have been performed with high concentrations of desipramine (10 microM) to define "specific binding," these data would suggest that either protease-sensitivity or displacability by 1 microM norzimeldine would give more reliable estimates of the specific binding.

Animals↗
PubMed1985

Memory function and brain biochemistry in normal aging and in senile dementia.

One might argue that the decrease in the number of brain cells as a function of age could be the source of the functional age deficits in memory performance. However, this possibility seems less likely since the actual loss of neurons up to advanced age is relatively small. There are no good estimates of the loss of synapses. Golgi staining of cortical neurons would indicate that there is a loss with higher age. So far, however, the most convincing data of marked loss with age appear at the biochemical level. Most human data fail to demonstrate a decrease in cholinergic and serotonergic activity as a function of normal aging, although there is a loss of corresponding receptors. In AD/SDAT, however, there is a marked damage to these systems. Conceivably, acetylcholine may be providing informational rather than tone setting or balancing influence on memory function. This may explain the failure of cholinomimetic drugs to improve memory in AD/SDAT due to their inability to supply the informational properties of normal neuronal transmission. The catecholamines, noradrenaline and dopamine are both lost in normal aging and to a much higher degree in AD/SDAT. Animal data show that noradrenaline deficiency results in scattered attention. Such a pattern might also exist in the intact aged and through guidance by means of instructions, contextual cues, and a richer TBR information, the elderly are being forced to attend. This may promote and supersede the normal functions of the noradrenaline system by directions from external rather than internal influences, conceivably by potentiating the remaining noradrenaline neurons. The cortical motor areas are relatively spared from neuro-degenerative changes in normal aging and in AD/SDAT and this might provide a neuroanatomical basis for the elderly's and mildly to moderately demented patients' success in memory performance when motor action is involved. The role of dopamine in motor function and its stability with age in hippocampus may also provide a neurochemical basis for the preservation of memory when the subjects are allowed to act physically during encoding.

Acetylcholinesterase↗
PubMed1985

The distribution of labeled antibiotics in normal and infected rat brain: an autoradiographic study.

The penetration and distribution of labeled benzylpenicillin and cefuroxime into normal and infected rat brain was studied. 15 rats were injected intravenously with radiolabeled antibiotic; 5 of these served as uninfected controls and 10 were previously infected by stereotactic deposition of 10(11) B. fragilis in the right frontal lobe inducing bacterial cerebritis. The animals were killed after administration of antibiotic. The brains were immediately frozen and cut into 20/micron sections. Autoradiographic recordings showed that benzylpenicillin was mainly distributed in the cerebrospinal fluid and pial vessels but no activity was found in the deeper grey or white matter. In contrast, cefuroxime was found not only in the surrounding but also in the centre of the infected area. The autoradiographic technique provides a valuable method for studies of the distribution of antibiotics in the brain.

Animals↗
PubMed1984

Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of S-2A sites with age.

Serotonin (S-2) binding sites were characterized in human frontal cortex and hippocampus throughout the lifespan. We found that the S-2 binding sites (labeled by [3H]spiperone and displaced by ketanserin) consisted of two subtypes (S-2A and S-2B) which are discriminated by competition with methysergide. The total S-2 sites in frontal cortex had a Bmax of 360 fmol/mg protein, which is approximately twice that of the hippocampus (160 fmol/mg protein). The density of total S-2 sites decreased with age in the frontal cortex of normal adults (17-100 years, n = 24). The receptor loss was primarily in the S-2A subclass. This loss of S-2A sites occurred primarily after 60 years and decreased to 50% of young adult values by the 10th decade. In the hippocampus, S-2A binding sites decreased with age, but no effects on total S-2 or S-2B sites were detected. A study of infant brains suggested the S-2A subtype in frontal cortex increases postnatally. However, in the infant hippocampus the S-2 binding approximated adult levels.

Adolescent↗
PubMed1984

Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multi-infarct dementia.

Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from age-matched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.

Brain Chemistry↗
PubMed1984

Personality traits related to monoamine oxidase activity in platelets.

Platelet monoamine oxidase (MAO) activity and intellectual level were examined in a large series of 1,129 18-year-old boys, selected from the general population. Personality traits were determined by means of selected subscales from several personality inventories such as the Zuckerman Sensation Seeking Scale, the Eysenck Personality Inventory, and the Karolinska Hospital Personality Inventory. Information was also gathered concerning alcohol consumption habits, signs of alcohol dependence, and use and abuse of tobacco, cannabis, glue, opiates, and amphetamine. Low MAO subjects were found to be more sensation seeking and to have higher scores on impulsivity and monotony avoidance. They also had higher use of tobacco and alcohol, showed more signs of possible alcohol dependence, and showed more drug abuse. When low MAO subjects were subdivided according to intellectual level, low MAO subjects with high intellectual level were found to have higher psychological functioning as judged by a psychologist after a clinical interview. Low MAO subjects with low intellectual level were found to have more use and abuse of alcohol and drugs, i.e., less accepted forms of sensation seeking, and they had a significantly lower level of psychological functioning. This subgroup seems to be the real "high risk" group that according to the high risk paradigm could be expected to show more alcohol abuse and higher tendencies to suicidal behavior.

Adolescent↗
PubMed1984

Serotonin concentrations in normal aging human brains: relation to serotonin receptors.

Concentrations of serotonin (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 7 regions of normal human brains and, in some of the regions, were compared to the number of serotonin receptors (S1 and S2). Neither 5-HT nor 5-HIAA concentrations correlated significantly with increasing age (from 17-100 years) in any of the regions investigated. Positive correlations between 5-HT and 5-HIAA were found in all regions studied, significantly (p less than 0.05) so in 5 of the areas. When comparing 5-HT transmitter and metabolite concentrations to the number of S1 and S2 receptors, no significant correlations were found either within any brain area of between different brain regions. These data confirm that 5-HT transmitter concentrations are not altered by increasing age, support the ideas that S1 and S2 receptors are not presynaptic and also that 5-HT transmitter concentrations and receptor densities are separately controlled.

Adolescent↗
PubMed1984

Effect of age on human brain serotonin (S-1) binding sites.

The effect of age on the binding of [3H]5-hydroxytryptamine [( 3H]5-HT, serotonin) to postmortem human frontal cortex, hippocampus, and putamen from individuals between the ages of 19 and 100 years was studied. One high-affinity binding site was observed in adult brains, with a mean KD of 3.7 nM and 3.2 nM for frontal cortex and hippocampus, respectively, and 9.2 nM for putamen. Decreased binding capacities (Bmax) with age were detected in frontal cortex and hippocampus. In putamen a decrease in affinity was noted. Postmortem storage did not significantly contribute to the age-related changes. No significant sex differences were detected. [3H]5-HT binding was also studied in brains from human neonates. The specific binding was 1.5-3 times lower than in adult frontal cortex and putamen, and Scatchard analysis suggested more than one binding site. In infant hippocampus a single binding site was observed and except for a premature individual, the binding capacity approximated adult values.

Accidents↗
PubMed1984

Dementia of the Alzheimer type and multi-infarct dementia: a clinical description and diagnostic problems.

Patients who had Alzheimer's disease-senile dementia of the Alzheimer type (AD/SDAT) or multi-infarct dementia (MID) were compared with a group of controls. Demented patients had approximately the same degree of dementia and the same duration of illness. The MID group had a significantly higher mean age than the AD/SDAT group. Sixty-three per cent of the AD/SDAT patients were free of other diseases, while 65 per cent of the MID patients had cardiovascular disease. Thirty per cent of the MID patients had a history of previous depression, while only 5 per cent of the AD/SDAT patients had had depression. At the time of the investigation, however, AD/SDAT patients showed significantly more signs of depression than the MID patients. Focal neurologic signs were found in 70 per cent of the MID patients and only 6 per cent of the AD/SDAT patients. The electrocardiogram was normal for every AD/SDAT patient, while 75 per cent of the MID patients had abnormal ECGs. Electroencephalography showed generalized slow frequencies in 79 per cent of the AD/SDAT patients and localized slow frequencies and abnormalities in 65 per cent of the MID patients. Computed tomography of the brain showed that MID patients had significantly greater dilation of the ventricular system, while cortical atrophy did not differ significantly among the three groups. Homovanillic acid in the cerebrospinal fluid was significantly lower in the AD/SDAT group as compared with controls.

Aged↗
PubMed1984

Progesterone distribution in the brain of the PMSG treated female rat.

The uptake of progesterone in the intact female rat brain was studied in 25, immature, female rats which were given an injection of 4 IU PMSG on the 25th day of life. The rats were killed 53-55 h after their first ovulation. Amounts of progesterone were measured in seven brain areas, peripheral fat and muscle tissue and blood plasma. The analyses were done by radioimmunoassay after extraction with ethanol or diethylether. The highest mean concentration was found in the cerebral cortex, followed by the hypothalamus, the hippocampus, the striatum, the midbrain, the cerebellum and the medulla oblongata (mean +/- SE pg/mg 29 +/- 2.0, 27 +/- 5.2, 19 +/- 2.4, 15 +/- 1.8, 14 +/- 2.0, 12 +/- 1.7 and 11 +/- 1.9). The concentration of progesterone in the cerebral cortex was significantly higher than in all other areas except the hypothalamus (p less than 0.001). The cerebral cortex, the hypothalamus and the hippocampus had progesterone levels that were significantly higher than in peripheral fat tissue (p less than 0.01). The plasma progesterone level correlated positively with that in the cerebral cortex (r = 0.62, p less than 0.01). Some earlier studies have shown high accumulation in the hypothalamus, but low in the cerebral cortex. One reason for the different results might be the nonphysiological models used in the earlier studies.

Animals↗
PubMed1984

Blood components in an elderly population.

The reference intervals of 18 blood components were established for an elderly population in the 8th decade of life. The most significant findings were a broader range of values for most of the components, lower values of plasma folate and plasma potassium and higher values of erythrocyte sedimentation rate, plasma creatinine and serum cholesterol, the lattermost in women only, compared to younger people.

Aged↗
PubMed1983

Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections.

The effects of aging on the total number and size of fibers, and the proportion and distribution of type 1 (slow twitch) and type 2 (fast twitch) fibers were studied in cross sections (15 mu thick) of autopsied whole m. vastus lateralis from two age groups. Each group consisted of six, previously physically healthy males (mean age 72 +/- 1 years and 30 +/- 6 years, respectively). The size of the muscles of the older individuals was 18% smaller (P less than 0.01) and the total number of fibers was 25% lower (P less than 0.01) than those of the young individuals (mean number 364,000 +/- 50,000 vs 478,000 +/- 56,000). There was, however, no significant difference in the mean fiber size (indirectly determined) or the proportion of the two fiber types, though a preferential reduction in type 2 fiber number in the aged individuals was seen. The relative occurrence of the fiber types at various depths in the aged muscles was found to be more even than in muscles from the young individuals. The results suggest that the aging atrophy in m. vastus lateralis, at least up to the age of 70, is primarily the result of a loss of fibers.

Adult↗
PubMed1983

Muscarinic receptor compensation in hippocampus of Alzheimer patients.

The activity of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) (presynaptic marker) and number of muscarine-like receptor binding sites have been measured in the hippocampus from eight individuals with senile dementia of Alzheimer type (SDAT) and ten controls. A negative correlation (r = 0.80; p less than 0.05) was found between the ChAT activity and the number of muscarine-like receptors in the SDAT group but not in the controls. The findings might indicate an ongoing compensatory receptor mechanism as a response to changes in presynaptic cholinergic activity.

Aged↗
PubMed1983

The activity of monoamine oxidase -A and -B in brains from chronic alcoholics.

The activity of monoamine oxidase--A was found to be lower in homogenates of hypothalamus and caudate nucleus, but not in cortex of the gyrus cinguli and hippocampus, from chronic alcoholics with respect to homogenates from autopsy cases without histories of alcohol abuse. The activity of monoamine oxidase--B was also lower in the alcoholics, but this could be due to the selective effect of age upon this enzyme form, since the alcoholics were younger than controls. No difference was found for either monoamine oxidase -A or -B activities in brain homogenates from an alcohol preferring (AA) strain of rats, with respect to those from a water preferring (ANA) strain.

Aged↗
PubMed1983

Serotonin binding in mouse brains. Some methodological aspects.

The binding of (3H)5-hydroxytryptamine ([3H]5-HT, serotonin) to crude homogenates of brains from three different strains of mice has been studied. The strains, C57/BL, DBA and BALB did not show significant differences in the binding characteristics, with Kd values around 6-7 nM and Bmax 270-310 fmoles/mg protein. Various methodological aspects were investigated and found to be important for the binding assay. The presence of ascorbic acid (5.7 mM) thus caused a significant increase in Bmax by 30% without any change in the Kd values. This increase seemed to be due to a decrease in the non-specific binding rather than to an increase in the total binding of serotonin. The presence of a specific MAO-A inhibitor, clorgyline (10 microM), during the assay, resulted in a significant reduction of Bmax by 20% without any change in the affinity for serotonin, when tissue which had been frozen was used. Less than 2% of added serotonin was metabolized during the binding procedure in the absence of clorgyline. Thus, the decrease in binding capacity caused by clorgyline, may be due to a non-competitive blocking effect of the serotonin binding structure. These results indicate that the use of MAO inhibitors in (3H)5-HT binding assays on frozen tissue, rather than being necessary, might negatively affect the result. Neither storage of the brains at -70 degrees nor postmortem storage of the animals for 60 hours at 4 degrees resulted in obvious changes in the (3H)5-HT binding characteristics.

Animals↗
PubMed1983

Changes in cholinergic activity in human hippocampus following chronic alcohol abuse.

Cholinergic mechanisms in the hippocampus seem to play a role in memory function. Since it is well known that chronic alcoholics often have a disturbed memory function, the cholinergic activity of the hippocampus has been measured in 20 chronic alcoholics and 14 controls, post-mortem. Of the alcoholics, 13 were classified as "intoxicated" alcoholics and 7 as "sober" alcoholics, i.e., without ethanol in blood or urine at the time of death. A lower, although not significantly lower activity of the enzyme choline acetyltransferase (ChAT, presynaptic marker) was measured in the hippocampus of the chronic alcoholics as compared to the control group. A trend towards a lower number of muscarine-like binding sites was also observed for the alcoholic group, but was only significant for the oldest group of alcoholics (59-68 years; -30%; p less than 0.01) in comparison to controls. No significant change in the number of nicotine-like binding sites was found. A normal aging process with degenerative nerve cell changes might, in combination with an excessive intake of ethanol, lead to the more pronounced decrease in muscarine-like binding sites found for the older alcoholics.

Aged↗