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O S Jørgensen

Publications and source records attributed to O S Jørgensen.

At least 19 recordsLinked to original sources
PubMed2006

No association between the -399 C > T polymorphism of the neuropeptide Y gene and schizophrenia, unipolar depression or panic disorder in a Danish population.

OBJECTIVE: A polymorphism in the promoter region of the NPY gene at position -399 C > T was recently reported to be associated with schizophrenia in a Japanese population and with treatment refractory unipolar depression in a Swedish population. The objective of this study was to investigate potential associations between the polymorphism and three psychiatric disorders in a Danish population. METHOD: We investigated the occurrence of the polymorphism in patients with schizophrenia (n = 291), unipolar depression (n = 256) and panic disorder (n = 142) compared with controls (n = 716). RESULTS: We detected the polymorphism -399 C > T at a frequency of 48% in controls. No significant differences were found between genotype or allele frequencies in controls vs. the patient groups. CONCLUSION: The lack of association between the -399 C > T polymorphism and schizophrenia, unipolar depression or panic disorder, respectively, suggests that the polymorphism is not involved in the etiology of these disorders in the Danish population.

Adult↗
PubMed2002

Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic markers (HLA-DRB1*1501, CCR5 deletion mutation, apolipoprotein E).

As the understanding of the autoimmune inflammatory response in multiple sclerosis (MS) expands, polymorphic genes involved in this process become possible candidates that may determine the severity of disease. Therefore, three candidate genes DRB1*1501, CCR5 and apolipoprotein E (APOE) were examined in a population-based patient sample (n = 70) to assess an association between disease progression measured by clinical disability and MRI parameters. The total lesion area (TLA) on T2-weighted images was measured with a semi-automated threshold technique. Patients with the CCR5delta32 allele showed a non-significant trend towards a smaller lesion burden (TLA/years duration), but were not associated to a milder EDSS/years duration. Our data support previous assumptions of a modulation of severity in MS by the CCR5delta32 genotype, which may convey less inflammation and tissue destruction. Carriers of the DRB1*1501 and APOE-epsilon4 allels did not reveal more severe disease progression, neither by the EDSS/years of duration nor by the TLA/years duration. This study was performed on a population-based sample in a genetically homogeneous Danish population but, due to the limited number of patients examined, weak associations between candidate genes and disease variables cannot be excluded.

Adult↗
PubMed2001

Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow.

The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age-stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE epsilon4-positive patients might predict clinical progression.

Age Factors↗
PubMed2000

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate.

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230

Adult↗
PubMed1999

Apolipoprotein E-epsilon 4 frequency in affective disorder.

BACKGROUND: The epsilon 4 allele of apolipoprotein E (APOE) as well as affective disorder have been found to be associated with Alzheimer's disease, but it is unclear whether cognitive impairment in affective disorder or subtypes of affective disorder is mediated by the epsilon 4 allele of APOE. METHODS: The genotype of APOE was analyzed in 106 unipolar patients, 21 bipolar patients, and 46 controls and correlated with cognitive function in the euthymic phase as measured by the Mini-Mental State Examination, the Cambridge Cognitive Examination, the Mattis Dementia Rating Scale, the Gottfries-Bråne-Steen Dementia Rating Scale, and the Global Deterioration Scale. RESULTS: The frequency of APOE-epsilon 4 allele was approximately the same in unipolar patients (.189) and in bipolar patients (.167). Although patients showed more cognitive impairment than controls, no significant overall difference was found between the frequency of APOE-epsilon 4 allele in patients (.185) and controls (.131). In fact, the frequency of APOE-epsilon 4 allele did not correlate with cognitive impairment. It was not possible to identify subgroups of patients with an increased frequency of APOE-epsilon 4 allele, as no association was found with gender, age at onset, the number of affective episodes, the presence of psychotic features, or the prevalence of familial affective disorder. CONCLUSIONS: It seems that cognitive impairment in affective disorder can be attributed to pathways other than the APOE genotype.

Adult↗
PubMed1999

[Comorbidity of infantile autism and blindness].

A three year-old girl with Leber's amaurosis was found to fulfil the criteria for autism, as will as being mentally retarded. Despite her blindness she displayed unusually by early motor development and was able to move around in her surroundings without difficulty. This case suggests that this ability was due to her relevant use of a minor visual remnant and, as is often seen in blindness, a capability of reflecting the surroundings--a "bat sense". The pervasive development a disorder influenced her abilities more strongly than her sensory handicap.

Autistic Disorder↗
PubMed1998

[Child psychiatric in-patient treatment].

This article describes the Danish part of a multinational epidemiological point-prevalence study concerning child psychiatric in-patient treatment, which aims to describe different kinds of treatment methods used in child psychiatric in-patient care. The study includes all 10 child psychiatric in-patient units in Denmark. Data on psychiatric treatment modalities were collected by means of a questionnaire in spring 1990 on 192 children, which included all of the actual in-patients (100%). Primary caretaking was the main treatment method (100%), individual psychotherapy was offered to one third, as was family therapy. Eight percent were medicated, 6% with psychoactive drugs. The study showed that medication in child psychiatric in-patient care was rare, and was never the only treatment method. A range of psychotherapeutic methods were used.

Adolescent↗
PubMed1997

Synaptic remodeling and free radical formation after brain contusion injury in the rat.

The purpose of this study was to explore whether bilateral frontal cortex contusion in rats would demonstrate changes relevant for understanding the pathology of frontal lobe injury in humans. Rats were allowed to survive for 3, 7, or 18 days postinjury (dpi). In the contused rats, albumin was trapped in frontal cortices, as well as in other brain areas, showing that neurons were exposed to plasma components. In the sham-operated rats, which had only craniotomy but no penetration of dura, the level of trapped albumin was also increased compared to intact controls, suggesting a partial lesion-like condition. Choline acetyltransferase activity was severely decreased in the frontal cortices of contused rats, compared to the sham-operated controls. The decrease was most pronounced at 3 dpi and less pronounced 18 dpi, suggesting that after the initial damage, regeneration of the cholinergic terminals occurred. The concentration of the mature presynaptic membrane protein D3(SNAP-25) was also decreased in the frontal cortices of contused rats at 3 and 7 dpi, whereas it was normalized at 18 dpi. Previously, we have evaluated changes in the rate of synaptic remodeling in brain injury by calculating the ratio of the neural cell adhesion molecule (NCAM) to D3(SNAP-25). The NCAM/D3(SNAP-25) ratio at 3 dpi was elevated by more than 60% in the frontal cortices of contused rats, suggesting a high initial rate of synaptic remodeling. The ratios were smaller at 7 and 18 dpi, suggesting that after the initial burst, the rate of remodeling leveled off. In contrast, astrocyte activation was less pronounced at 3 dpi than at 7 and 18 dpi, as measured by the levels of glial fibrillary acidic protein and glutamine synthetase immunoactivities. The immunoreactivity of glutamine synthetase more than doubled in the contused brains but its enzymatic activity increased less than 50%, suggesting that many enzymatic centers had been inactivated by free radicals. Calculated as the difference between the relative immunoreactivity and the relative enzymatic activity the "lost glutamine synthetase activity" increased continuously in frontal cortex and striatum from 3 to 18 dpi, indicating the production of free radicals long after the initial contusion event. In conclusion, following frontal cortical contusions the early synaptic damage was partly compensated by synaptic remodeling. We suggest that the continuous production of free radicals may have contributed to the declining remodeling rate and impair functional recovery.

Animals↗
PubMed1997

Weaver mutant mouse cerebellar granule cells respond normally to chronic depolarization.

We studied the effects of chronic K(+)-induced membrane depolarization and treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule cells (CGCs) from weaver mutant mice and non-weaver litter-mates. The weaver mutation is a Gly-to-Ser substitution in a conserved region of the Girk2 G protein-coupled inward rectifying potassium channel [Patil N., Cox D. R., Bhat D., Faham M., Myers R. M. and Peterson A. S. (1995) Nature Genet. 11, 126-129] which induces early death of CGCs. The biochemical differentiation of CGCs was estimated as the rate of 2-deoxy-D-glucose accumulation and the expression of neural cell adhesion molecule (NCAM). High (25 mM) K+ ion concentration or treatment with NMDA greatly promoted the biochemical differentiation of both weaver mutant and non-weaver litter-mate mouse CGCs. In contrast to the marked effect on biochemical differentiation in both weaver and non-weaver mice CGSs, chronic high K+ treatment only had limited effect on survival. The survival of weaver mutant mouse CGCs in medium containing 5 mM K+ ions was very low, only 20% of the plated cells surviving at 7 days after plating, as opposed to the 50% for non-weaver CGCs. Chronic high K+ treatment improved the relative survival of weaver mutant mouse CGCs 1.6 2.2-fold and that of non-weaver CGCs 1.2-1.4-fold; the same number of CGCs (about 20% of the plated cells) were rescued by high K+ in both types of culture. The findings indicate that, in culture weaver mutant mouse, CGCs have a normal response to membrane depolarization and that the normal function of the Girk2 potassium channel is not critical for the survival of differentiated CGCs.

Animals↗
PubMed1996

Synaptic degeneration and remodelling after fast kindling of the olfactory bulb.

Kindling of the olfactory bulb using a novel fast protocol (within 24 h) was studied in rats. In target brain regions, the effects of kindling were measured on the concentration of glial fibrillary acidic protein (GFAP) by dot-blot and on the concentrations of neural cell adhesion molecule (NCAM) and the 25 kDa synaptosomal associated protein of the D3 immunoprecipitate (D3(SNAP-25)) by crossed immunoelectrophoresis. Bilateral increases in the levels of GFAP, indicating activation of astrocytes, were detected in primary olfactory cortical projection areas, including the piriform cortex, and also in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling. At this time, however, an overall pattern of ipsilateral decreases in the synaptic marker proteins NCAM and D3(SNAP-25) indicated that this remodelling occurred on a background of synaptic degeneration. These results confirm previous studies showing that kindling is associated with synaptic remodelling and neuronal degeneration in the hippocampal formation and extends the area of plasticity to include the piriform cortex which is believed to be central to the kindling process.

Animals↗
PubMed1996

NMDAR1 mRNA expression and glutamate receptor stimulated increase in cytosolic calcium concentration in rat and mouse cerebellar granule cells.

We have previously reported that, unlike their rat counterparts, the survival of mouse cerebellar granule cells is independent of chronic stimulation whether owing to elevated K(+)-induced depolarization or NMDA (N-methyl-D-aspartate) receptor activation. One explanation could be that during the critical period mouse granule cells are very sensitive to NMDA receptor stimulation by endogenous glutamate released in the cultures. If so, this might be reflected by an increased expression of NMDA receptors or an increased response to their activation. We tested this hypothesis by measuring (a) the concentration of mRNA for the obligatory NMDA receptor subunit, NMDAR1, and (b) the glutamate/NMDA stimulated increase in cytosolic Ca(2+)-ion concentration in cultures at physiological or elevated K(+)-ion concentration. The expression of NMDAR1 mRNA was measured by competitive PCR of reversely transcribed mRNA and was normalized to that of the constitutively expressed H3.3 histone mRNA. The glutamate and NMDA stimulated increase in cytosolic Ca(2+)-ion concentration was measured using the fluorescent Ca(2+)-chelator Fluo3. In contrast to the hypothesis, we found NMDAR1 mRNA expression to be lower in mouse than in rat granule cells cultured for 4 days at physiological K(+)-ion concentration. However, the NMDA stimulated increase in cytosolic Ca(2+)-ion concentration did not differ in 4-day rat and mouse cultures. Although the glutamate-stimulated increase in cytosolic Ca(2+)-ion concentration in 2-day cultures was higher in mouse granule cells than in rat granule cells, the developmental profile of the glutamate-stimulated increase in cytosolic Ca(2+)-ion concentration was the same in both cases. In conclusion, we found no obvious evidence for increased NMDA receptor activity in mouse cerebellar granule cells cultured at physiological K(+)-ion concentration.

Aniline Compounds↗
PubMed1995

SNAP-25 is the major immunoreactive component of the brain-specific D3 protein.

The rat synaptosomal membrane antigen D3, which has been studied for more than 20 years since its first demonstration as a brain-specific protein, was shown to bind monoclonal antibodies to SNAP-25, a presynaptic plasma membrane-associated protein. In addition to SNAP-25, anti-D3 antiserum also precipitated two polypeptides of 34-36 kDa and 14-16 kDa. This suggests that anti-D3 binds all three of the 20S synaptic vesicle fusion particle components, i.e. SNAP-25, syntaxin, and vesicle-associated membrane protein (VAMP)/synaptobrevin. However, the botulinum toxins C and D, which are endoproteases selective for syntaxin and VAMP/synptobrevin, respectively, were unable to remove the D3 immunoreactivity from synaptosomal membranes. Therefore, it is concluded that D3 immunoreactivity is directed only against SNAP-25.

Amino Acid Sequence↗
PubMed1995

Neural cell adhesion molecule (NCAM) as a quantitative marker in synaptic remodeling.

The neural cell adhesion molecule (NCAM) participates in adhesion and neuritic outgrowth during nervous system development. In the adult brain, NCAM is considered to be involved in neuronal sprouting and synaptic remodeling. The NCAM concentration of brain tissue has proved to be a useful marker of these processes, especially when viewed in comparison with the concentration of a marker of mature synapses, e.g. D3-protein (SNAP-25) or synaptophysin. The present review focusses on studies of adult brain in which NCAM concentration estimates and NCAM/D3 ratios have been used to evaluate the rate of synaptic remodeling in brain damage and degenerative diseases.

Animals↗
PubMed1994

Ontogeny of the cell adhesion molecule L1 in the cerebellum of weaver and reeler mutant mice.

The ontogeny of cell adhesion molecule L1 in cerebellum was quantitatively assessed in weaver and reeler mutant mice and in heterozygous litter-mate controls. In the latter the concentration and the amount of L1 both increased from the first postnatal week to become maximum at the second. In contrast, in the weaver and reeler neurologic mutant mice, L1 decreased steadily. The L1 concentration and the amount of L1 was lower in the cerebellum of homozygous mutant mice than in litter-mate controls. The findings are consistent with L1 being a component of axonal plasma membranes. However, no evidence was found of any direct effect of the wv and rl phenotypes on L1 expression.

Animals↗
PubMed1994

Repeated electroconvulsive shock selectively increases the expression of the neuron specific enolase in piriform cortex.

The effect of repeated electroconvulsive shock (ECS) on the activities of the three enolase isoenzymes present in rat brain: neuron specific enolase (NSE), non-neuronal enolase (NNE) and the hybrid enolase was investigated in piriform cortex. The activities were estimated on isoenzymes separated by agarose gel electrophoresis. Whereas the specific activities of NNE and hybrid enolase were unchanged in piriform cortex or ECS-treated rats the specific activity of NSE was increased by 16.3 percent (P < 0.02). The brain enolase isoenzymes are dimers of alpha- and gamma-enolase subunits. The calculated ratio between the gamma-subunit present in both NSE and hybrid enolase and the alpha-subunits present in both NNE and hybrid enolase was increased by 11.7 percent in piriform cortex of ECS-treated rats (P < 0.05). Previously, it has been shown that the gamma-subunit is only expressed in neurons whereas the alpha-subunit is expressed in both neurons and glial cells. The selectively increased expression of the enolase gamma-subunit in ECS-treated rats might either reflect an increased transcription of a whole group of neuronal genes or rather the trophic role of NSE in ECS-enhanced synaptic remodelling of the rat brain.

Animals↗
PubMed1994

Electroconvulsive stimulations, learning, and protein changes in the rat brain.

Two groups of rats were subjected to 17 training sessions on an operant task demanding the sequential operation of two manipulanda, while two other groups were left with no training experience. Within both the trained and passive groups one was exposed to a series of 12 electroconvulsive stimulations. The series of training and stimulation sessions were concurrent but arranged in such a way that at least 24 h always separated training and stimulation. Upon completion of the behavioural part of the experiment the concentrations of the marker proteins neural cell adhesion molecule (NCAM), D3, synaptophysin, and S100 were estimated in the prefrontal and occipital parts of the cortex, the hippocampus, and in the total forebrain. The electroconvulsively stimulated animals demonstrated severe impairment of learning. The pattern of marker protein concentrations indicated that acquisition and/or performance of the task and exposure to electroconvulsive stimulation were both accompanied by similar patterns of synaptic changes: an increased concentration of small synaptic vesicles in both the prefrontal cortex and the total forebrain and an increased synaptic remodulation in the prefrontal cortex.

Animals↗