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Biomedical subjects

L Oreland

Publications and source records attributed to L Oreland.

At least 109 records · Page 6Linked to original sources
PubMed1994

Brain ATP:L-methionine S-adenosyltransferase (MAT), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH): regional distribution and age-related changes.

The distribution of the activity of the enzyme methionine adenosyltransferase (ATP:L-methionine S-adenosyltransferase, EC 2.5.1.6, MAT) was investigated in human postmortem brains of individuals without a known history of neuropsychiatric disorders. The brain regions were the frontal, temporal, parietal and occipital cortices, nucleus caudatus, putamen, globus pallidus, thalamus and white matter. The activities in the nucleus caudatus and putamen were approximately 25% higher than the activities in the seven other brain regions, however, not on a statistically significant level. The apparent values of MAT Km and Vmax in the parietal cortex were 11.41 +/- 3.51 microM methionine and 25.72 +/- 3.90 nmol/mg protein/h, respectively. In the frontal cortex, a significant positive correlation between age and the activity of MAT was found (r = 0.997, P < 0.01). Concerning MAT stability in the rat brain, there was a steady decrease in the activity with postmortem time in the brains kept for 0-72 h at room temperature (23 degrees C), which reached the level of significance at 24 h. The activity did not change significantly when the brains were kept for 120 h at 4 degrees C, or by freezing and thawing the tissue before analysis. In a parallel study in rats of different ages (2-22 months), a homogeneous distribution of SAM and SAH was observed in the cortex, striatum, midbrain, hypothalamus, brainstem and cerebellum. The lowest levels of SAM and the highest levels of SAH observed in the striatum gave the lowest SAM/SAH ratio. The SAH content of rat cerebral cortex was highest in the oldest group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Criminality and platelet monoamine oxidase activity in former juvenile delinquents as adults.

Platelet monoamine oxidase (MAO) activity was estimated in 70 former delinquent boys and 40 controls now aged 38-46 years. Platelet MAO activity was compared with their early criminal behaviour (before the age of 15) and their late registered criminality from the age of 15). Mean platelet MAO activity in subjects with both early and late criminality was significantly lower than that in former delinquents without late criminality. There was no significant difference in mean platelet MAO activity between controls and delinquents with early but no late criminality. When delinquents with early criminality were divided into a low and a high MAO group, the relative risk to be registered for late criminality was about 3.1 times higher for the subjects in the low MAO group. Thus, individuals with low platelet MAO activity run an increased risk of continued criminal behaviour.

Adolescent↗
PubMed1994

Alcoholics with reduced dopamine D2 receptor function possess normal platelet monoamine oxidase activity.

Platelet monoamine oxidase (MAO) activity, proposed to be a marker for central 5-hydroxytryptamine (5-HT) capacity, was investigated in 14 severely alcohol-dependent subjects with reduced dopamine (DA) D2 receptor function, as assessed by the growth hormone responses to apomorphine. Twelve healthy men were used as controls. Platelet MAO activity in the alcohol-dependent subjects was not different from that in controls. The finding from this preliminary study suggests that severely alcohol-dependent subjects with reduced DA D2 receptor function have normal 5-HT capacity.

Adult↗
PubMed1994

Cholecystokinin receptor binding after long-term ethanol treatment in rats.

Brain cholecystokinin (CCK) receptors have been implicated in anxiety disorders and suicidal behaviour. We have examined the radioligand binding ability of CCK and benzodiazepine receptors in rat brain after long-term intermittent voluntary vs voluntary and forced low-dose ethanol exposure. During 58 weeks, one group of rats had a choice between ethanol and water as the drinking fluid for 24 hr each week. Another group of rats had the same weekly choice between ethanol and water, but at the end of each 24 hr choice period, ethanol (2.0 g/kg) was injected. During the second period of ethanol treatment, lasting for 32 weeks, both ethanol-treated groups had continuous free access to ethanol and water. These two treatments have previously been shown to induce partially different neurochemical alterations. In the present investigation, benzodiazepine receptor binding in the frontal cortex, hippocampus and striatum was similar in both ethanol treatment groups compared to controls. CCK receptor binding in the hippocampus and striatum did not differ between the three groups; however, in the frontal cortex, there was an increase in the apparent number of CCK binding sites in the group of rats submitted to voluntary plus forced ethanol exposure as compared to the control group or the voluntary intake group. These results suggest that long-term ethanol treatment may lead to alterations in brain CCK-ergic neurotransmission, but that the changes are specific to the treatment schedule.

Alcoholism↗
PubMed1993

Monoamine oxidase-B in astrocytes.

In the present report we describe the astrocytic localization and content of monoamine oxidase-B (MAO-B) by means of a 3H-L-deprenyl emulsion autoradiography in primary cultures of rat astrocytes, in cryosectioned astrocytoma surgical specimen, and in cryosections of human spinal cords from patients dying in amyotrophic lateral sclerosis (ALS) and controls. The occurrence of MAO-B enzyme protein depends on the degree of cellular differentiation as demonstrated by studies on astrocytes in primary cultures analyzed at two different stages of maturation. Highly differentiated cells exhibited high relative enzyme concentration whereas glioblasts lacked or showed very low contents of MAO-B enzyme. This was further substantiated by studies performed on human astrocytoma tissue using 3H-L-deprenyl emulsion autoradiography in combination with immunohistochemical detection of glial fibrillary acidic protein (GFAP). Regional increases of MAO-B concentration were found in ALS lumbar sections with quantitative 3H-L-deprenyl autoradiography. On the basis of results obtained from double staining for GFAP and MAO-B, the increase in MAO-B seemed to be due to an increased number of astrocytes as well as an increased content of MAO-B in reactive species of astrocytes. A cell culture model has been used that produces cells with morphology and GFAP-content similar to reactive cells. These astrocytes exhibited high relative content of the MAO-B enzyme protein. In the light of the presented data, taking into account the finding that a subpopulation of reactive cells contained low levels of MAO-B, a heterogeneity among reactive astrocytes was observed.

Amyotrophic Lateral Sclerosis↗
PubMed1993

Social isolation of rats increases the density of cholecystokinin receptors in the frontal cortex and abolishes the anti-exploratory effect of caerulein.

The role of cholecystokinin (CCK) receptors in the development of anxiety caused by social isolation of rats was studied using the elevated plus-maze and receptor binding techniques. The isolation of male Wistar rats significantly reduced their exploratory activity in the elevated plus-maze compared with that of rats kept in groups of four. Caerulein (0.1-5 micrograms/kg s.c.), an agonist at CCK receptors, only at the highest dose (5 micrograms/kg) significantly decreased the exploratory behaviour of rats housed in groups, but not in the isolated rats. By contrast, small doses of caerulein (0.1-0.5 microgram/kg) even tended to increase the behavioural activity of isolated rats in the plus-maze test. In parallel to the behavioural changes, isolation of the rats increased the number of [3H]pCCK-8 binding sites in the frontal cortex, but not in the other forebrain structures (the mesolimbic area, striatum and hippocampus). Isolation did not affect the density of benzodiazepine receptors in the frontal cortex. In conclusion, the isolation of rats for 7 days produced anxiogenic-like effect on the behaviour of rats and increased the number of CCK receptors in the frontal cortex without affecting benzodiazepine receptors.

Animals↗
PubMed1993

CCKB receptor activation reduces glutamate-induced depolarization in slices of rat cerebral cortex.

Recent studies on cell cultures have indicated that the neuropeptide cholecystokinin (CCK) can prevent glutamate-induced cytotoxicity. In a preparation of rat cortical tissue placed into a two-compartment bath, the cortical tissue could be depolarized, relative to the corpus callosum, by superfusions of KCl or glutamate (1.25-10 mM). Caerulein (1-100 nM), a CCK receptor agonist, caused a rightward shift of the glutamate dose-response curve. The effect of caerulein was abolished by adding L365,260 (1 microM), a selective CCKB receptor antagonist. These findings suggest that CCK may be a physiological antagonist of glutamate-mediated neurotransmission in the rat brain.

Animals↗
PubMed1993

Cholecystokinin receptors and memory: a radial maze study.

CCK receptor agonists and antagonists have repeatedly been demonstrated to improve and impair, respectively, learning and memory functions. However, all studies to date have exploited avoidance paradigms. In the present study, the effect of some CCK receptor agonists and antagonists on the ability to learn an appetitively motivated task and to influence spatial working memory was investigated. In the first experiment, drugs were given immediately after each training session in the radial maze and the animals were tested, drug-free, during a 2-week period. After the initial treatments with caerulein, an unselective CCK receptor agonist (100 ng/kg SC), the animals were slightly less successful to obtain food pellets during the sessions on the first 2 days; whereas proglumide, an unselective CCK receptor antagonist (1 mg/kg SC) was without any effect. However, on the following days, all the three groups of rats (saline, caerulein, and proglumide) performed in a similar way. In the second experiment, drugs were given before each test session to well-trained animals. Scopolamine (0.15 and 0.3 mg/kg IP), the reference amnestic drug, produced dose-dependent impairment of working memory in the radial maze test. Proglumide (1 and 10 mg/kg SC) and devazepide, (a selective CCK-A receptor antagonist; 0.01 and 1 mg/kg SC), as well as caerulein (0.01, 0.1 and 1 microgram/kg SC) and CCK-4 (a selective CCK-B receptor agonist; 25 and 50 micrograms/kg SC) had no reliable effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together.

The relative importance of shared genes, shared environments, and individual specific environmental effects for monoamine oxidase (MAO) activity in thrombocytes was assessed in the Swedish Adoption/Twin Study of Aging. The sample consists of identical twins separated at an early age and reared apart (30 pairs), identical twins reared together (60 pairs), fraternal twins reared apart (66 pairs), and fraternal twins reared together (68 pairs), whose average age was 63.5 years; 49% were female. Consistent with the literature, the heritability of MAO activity was 0.77 and did not differ across cohort (under or over 63 years of age) or gender. Sharing rearing environments or similar experiences later in life does not result in familial similarity for MAO activity.

Adoption↗
PubMed1993

gamma-Aminobutyrate aminotransferase activity in blood platelets of six species.

1. The kinetic parameters of gamma-aminobutyrate aminotransferase (GABA-T) were studied in washed blood platelets from cat, dog, horse, man, mouse and rat. 2. Wide differences were found in the maximal reaction velocity (Vmax) of GABA-T in blood platelets of the six species. 3. A significant increase in the activity of GABA-T was found in the blood platelets of adult rats as compared to those of young rats. 4. However, there was no significant difference in the activity of platelet GABA-T between male and female rats. 5. The activity of human platelet GABA-T estimated in platelet-rich plasma from healthy male subjects was found to be decreased in the presence of plasma and albumin. 6. The decrease was due to the specific binding of the cofactor pyridoxal phosphate to plasma albumin.

4-Aminobutyrate Transaminase↗
PubMed1993

Brain GABA-transaminase and monoamine oxidase after chronic ethanol treatment in rats.

The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO-A and -B) were estimated in various brain regions of rats exposed to ethanol for 90 weeks. During the first period (weeks 1-58), the rats had access to both ethanol (10% w/v) and water during a 24-hr interval at the end of each week. At this point, the animals were given either a saline injection (intraperitoneally, group 1) or an ethanol injection (2.0 g/kg ip, group 2). During the second period (weeks 59-90), the rats in groups 1 and 2 had continuous access to both ethanol and water. The third group was composed of untreated control rats. Compared with controls, there was an increase of 20-45% in the mean brain GABA-T activity in both groups of ethanol-treated rats. However, analysis of the data for the individual ethanol-treated rats revealed a considerable difference in brain GABA-T activity. Thus, approximately 30% of the ethanol-treated rats showed approximately twice the activity of rats in the exposed groups and in the control group. There was no connection between ethanol intake, water intake, or body weight and GABA-T activity in any of the brain regions examined. There was no effect of ethanol in vitro on the activity of GABA-T in the brain cortex in concentrations of 20-100 mM, whereas acetaldehyde inhibited the activity by 15% at these concentrations. The present results suggest that there is a bimodal distribution with respect to the effect of ethanol on rat brain GABA-T activity.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗
PubMed1992

Changes in cholecystokinin receptor binding in rat brain after selective damage of locus coeruleus projections by DSP-4 treatment.

Brain cholecystokinin (CCK)- and noradrenergic activities are two neurochemical systems implicated in anxiety and deficits in novelty-related behaviour. In order to clarify a possible interaction between CCK- and noradrenergic neurotransmission in the brain, DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a neurotoxin that selectively destroys noradrenaline-containing nerve terminals originating from the locus coeruleus, was administered to rats IP (10 and 50 mg/kg) seven days before decapitation. Noradrenaline uptake was very markedly reduced in the frontal cortex and hippocampus of the DSP-4 treated animals, whereas the decrease in the hypothalamus was smaller but still statistically significant. Dopamine uptake in the corpus striatum, as well as serotonin uptake in the frontal cortex, hippocampus and hypothalamus, were not influenced by DSP-4 treatment. Concomitantly, CCK receptor binding in certain brain regions was markedly affected. Thus, CCK receptor density was significantly higher in the frontal cortex and hippocampus of DSP-4-treated rats. If desipramine (25 mg/kg) was administered before DSP-4 treatment, the DSP-4-induced changes both in noradrenaline uptake and CCK receptor binding were not present, suggesting that both effects were exerted after uptake of the neurotoxin by the nerve terminals. The time-course of the development of changes in CCK-8 binding paralleled with some lag the development of changes in noradrenaline uptake. These findings demonstrate the denervation of noradrenergic input from the locus coeruleus induces certain alterations in the CCKergic neurotransmission. These alterations are similar to those seen in rats with deficits in response to novel stimuli, and may therefore mediate the neophobic responses observed in animals after lesions of noradrenergic innervation of the forebrain.

Animals↗
PubMed1992

Gamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients.

The activity of gamma-aminobutyrate aminotransferase (GABA-T) was estimated in twelve regions of brains from 22 control subjects and 6 cases with schizophrenia. In the controls, no significant correlation was found between the enzyme activity and age or postmortem interval (PMI) in any of the brain regions studied. In experiments on rat brains, the enzyme activity decreased about 20% during the first 2 hours of storage at room temperature and at 4 degrees C but remained steady thereafter. A similar initial decline in activity in the human brain material cannot be excluded. In the human brains, a slightly lower activity was found in the group below 75 years (n = 8) when compared with the group above 75 years (n = 8). A tendency to higher activities was found in female brains (n = 10) compared with male brains (n = 12). No significant difference in the enzyme activity was found between schizophrenic brains, in any of the regions studied, when compared to controls, matched for age, sex and PMI.

4-Aminobutyrate Transaminase↗
PubMed1992

Brain gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer's disease.

Activities of Gamma-aminobutyrate aminotransferase (GABA-T) and Monoamine oxidase (MAO)-A and -B were estimated in postmortem brains from 6 control subjects without psychiatric or neurologic disorders and 8 histopathologically verified cases of patients with Alzheimer's disease and senile dementia of Alzheimer type (AD/SDAT). The enzyme activities were examined in four cortical brain regions, three nuclei in the basal ganglia, thalamus and white matter. GABA-T activities in the cortical regions (frontal, parietal, occipital and temporal cortices) and nucleus caudatus were significantly lowered in the AD/SDAT patients. The MAO-A activities were significantly increased in the occipital cortex, caudate nucleus, thalamus and white matter in the AD/SDAT patients. No significant differences were found in the other regions (frontal cortex, parietal cortex, temporal cortex, putamen and globus pallidus). The MAO-B activities in three cortical regions (frontal, parietal and occipital cortices), thalamus and white matter were significantly increased in the AD/SDAT patients, whereas no difference was apparent in the other regions. The changed activities could not be correlated with age or postmortem time. The present results are the first describing decreased GABA-T activities as well as increased MAO-A activities in brain from patients with AD/SDAT, while the results with MAO-B support previous findings. A possible connection was found between the order of magnitude of the changes in enzyme activities and the severity of the disease.

4-Aminobutyrate Transaminase↗
PubMed1992

Age-related differences of cholecystokinin receptor binding in the rat brain.

1. Cholecystokinin and benzodiazepine receptor binding was evaluated in 2-, 9- and 18-month old rats in the brain regions where cholecystokinin octapeptide and gamma-aminobutyric acid are known to coexist in common nerve cells (frontal cortex, hippocampus). 2. There was a regionally selective alteration of hippocampal 3H-CCK-8 binding in the oldest age group, if compared to both young and adult animals. Non-linear regression analysis of binding data revealed significantly lower apparent number of binding sites (Bmax), and twofold (but not statistically significantly) higher binding affinity for the radiolabelled ligand. No differences between any age groups in 3H-flunitrazepam binding to benzodiazepine receptors were found. 3. The results suggest that changes in cholecystokinin receptor characteristics might contribute to the behavioural impairments in aged rats.

Aging↗
PubMed1992

Monoamine oxidase-B in motor cortex: changes in amyotrophic lateral sclerosis.

The occurrence of monoamine oxidase-B in cerebral cortex and white matter in brains from three patients with the diagnosis of amyotrophic lateral sclerosis and three controls was quantified by means of an autoradiographical method. [3H]L-Deprenyl, an irreversible and selective monoamine oxidase-B inhibitor, was used as ligand and the autoradiographs were analysed by computer-assisted densitometry. In both amyotrophic lateral sclerosis and control cerebral cortex, lamina I showed the highest, laminae II and III intermediate, laminae IV, V and VI the lowest [3H]L-deprenyl binding. White matter showed about one-third of the binding in the cortex. Amyotrophic lateral sclerosis cases showed significantly higher binding of [3H]L-deprenyl in all the cortex laminae of the pre- and postcentral gyri. There was no difference in the binding between the amyotrophic lateral sclerosis cases and the controls in area 7 of the occipital cortex, an area which is relatively spared in amyotrophic lateral sclerosis.

Aged↗