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A Nordberg

Publications and source records attributed to A Nordberg.

At least 19 recordsLinked to original sources
PubMed2003

Cerebral glucose metabolism, cerebrospinal fluid-beta-amyloid1-42 (CSF-Abeta42), tau and apolipoprotein E genotype in long-term rivastigmine and tacrine treated Alzheimer disease (AD) patients.

We evaluated cerebral glucose metabolism (CMRglc) and cerebrospinal fluid (CSF) levels of tau and beta-amyloid(1-42) (Abeta42), in relation to apolipoprotein E (ApoE) genotype, in patients with mild Alzheimer disease (AD) treated with rivastigmine (n=11) and tacrine (n=16) for 1 year; and two untreated AD groups. The rivastigmine-treated AD patients showed a significant increase in CMRglc as compared to both tacrine-treated and untreated AD subjects. The rivastigmine-treated AD group showed no change in CSF-tau levels after 1 year, while in contrast a significant increase as seen in tacrine-treated and untreated AD patients. The CSF-tau changes were mainly seen in ApoE epsilon4 carriers. There was no significant change in Abeta42 after 1-year treatment with either rivastigmine or tacrine. This study shows that the two long-term cholinesterase inhibitor treatments exert different effects on biological markers for AD.

Aged↗
PubMed2002

Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months.

OBJECTIVE: To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with AD. METHODS: Eleven patients with mild AD received rivastigmine for 12 months. Cholinesterase (ChE) activities in the CSF and plasma were assessed colorimetrically. Immunoblot analysis was used to evaluate AChE isoforms. Neuropsychiatric tests were performed throughout the study. RESULTS: At 12 months, the mean dose of rivastigmine was 8.6 mg/d and specific activities of ChE in the CSF were lower than baseline values (by 36% for AChE and 45% for BuChE), correlating with parallel reductions in the plasma (27% for AChE and 33% for BuChE). The reduction of specific activities in the CSF, but not in the plasma, appeared to be dependent on the dose and duration of treatment. Scores of some of the neuropsychological tests associated with memory and attention were correlated with both plasma and CSF AChE and BuChE inhibition for up to 6 months. Immunoblot analysis revealed up-regulation of the "read-through" AChE isoform (AChE-R), whereas levels of the synaptic isoform were unchanged. CONCLUSIONS: Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased AChE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the AChE-R isoform may have a favorable effect on disease stabilization.

Acetylcholinesterase↗
PubMed2002

Chronic treatments with tacrine and (-)-nicotine induce different changes of nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.

The present study evaluated effects of chronic treatment with tacrine and (-)-nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the brains of old rats (24-25 months) by receptor autoradiography. The nicotinic receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was observed in all of the brain regions analysed following chroinic treatment with tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in most of the brain regions analysed except for a few brain regions where a decrease was observed in tacrine treated animals compared to control animals. Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions analysed except for the hippocampus when measured by (-)-[3H]nicotine. A significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding was observed in all of the brain regions analysed following the treatment with tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine differentially interfere and regulate the subtypes of nAChRs and mAChRs in the brain of aged rat. These data differ from what have been earlier observed in the brain of young adult rat following tacrine treatment, revealing some dynamic changes in receptor properties in the brain during aging.

Aging↗
PubMed2002

Early warning of disturbances in a laboratory-scale MSW biogas process.

The use of near-infrared spectroscopy (NIR) to monitorthe dynamics of a biogas process was evaluated using multivariate data analysis. The digester was a completely stirred 8 I tank reactor fed with the organic fraction of source-sorted MSW. Intermittently the digester was overloaded with feed. Before and after overload on-line monitoring of NIR spectra and off-line analysis in the liquid and the gas phase of traditional chemical variables and microbial biomass, determined as total concentration of phospholipid fatty acids (PLFA and PLEL), were done. The dynamics that occurred due to overloading could be followed using principal component analysis of the obtained NIR-spectra. In addition, the response to changes in the digester fluid was reproducible and could be detected within five minutes, which can be considered as real-time monitoring. Selected wavelengths in the region 800-2,000 nm were used to make a PLS1 -regression with propionate. The regression resulted in a good correlation for propionate (R= 0.94 and RMSEP of 0.21 g/l in the range of 0.3-3 g/l). The results indicate the possibility to develop an early warning biogas control system based on near-infrared spectroscopy monitoring of propionate.

Automation↗
PubMed2001

Expression of nicotinic acetylcholine receptors in human and rat adrenal medulla.

Neuronal nicotinic receptors (nAChRs) are expressed in the brain but also in the peripheral tissues including the adrenal medulla. However, it is unclear which nAChRs are present in the human adrenal medulla. In the study, receptor binding assay, Western blot and RT-PCR have been performed to investigate the expression of nAChRs in adrenal medulla from human, rat and mouse. The results showed that in human adult adrenal medulla, mRNAs for nAChR alpha3, alpha4, alpha5, alpha7, beta2, beta3, and beta4 subunits but not beta2 in the fetal human adrenal medulla were expressed. Saturation binding of [3H]epibatidine showed two binding sites in human aged adrenal medulla. The specific binding of [3H]epibatidine (0.1 nM) was significantly higher in human fetal compared to human aged adrenal medulla. mRNAs for the alpha3, alpha4, alpha5, alpha7, beta2, and beta4 subunits but not the beta3 were detectable in adult rat and mouse adrenal medulla. No differences in gene-expression of the nAChRs were observed between new born, adult and aged rat adrenal medulla. Saturation binding of [3H]epibatidine showed only one binding site in rat adrenal medulla. Lower protein levels for the nAChR subunits were observed in the rat adrenal medulla compared to rat brain. There was lower protein levels of the nAChRs in aged rat adrenal medulla compared to the young rats. Sub-chronic treatment of nicotine to rats did not influence level of the nAChRs in the adrenal medulla. In conclusion, the expression of nAChRs in adrenal medulla is age- related and species dependent.

Adrenal Medulla↗
PubMed2001

Reduced expression of neuronal nicotinic acetylcholine receptors during the early stages of damage by oxidative stress in PC12 cells.

The mechanism for a large loss of neuronal nicotinic acetylcholine receptors (nAChRs) in brains with neurodegenerative diseases remains unclear. Based on our previous results of [(3)H]epibatidine binding influenced by lipid peroxidation, we suggest that nAChR deficit in neurodegenerative diseases might be related to the neurons attacked by free radicals. To further understand how free radicals influence the expression of nAChRs, we detected [(125)I]alpha-bungarotoxin binding, nAChR subunit protein and mRNA during the early stage of damage by oxidative stress in PC12 cells in the present study. The results showed that free radical insult (FeSO(4)) within the concentration range (1 -100 microM) used in the study induced dose-dependent increases in lipid peroxidation and toxicity to PC12 cells, but did not result in apoptosis or necrosis. Significant reductions in [(125)I]alpha-bungarotoxin binding site, protein level for the alpha3 and alpha7 subunits, and mRNA level for the alpha7 subunit were observed in PC12 cells treated by FeSO(4) at the concentrations without inducing cell death compared to control. Pretreatment of cultural cells with antioxidant such as Vitamin E and reduced glutathione prevented the inhibiting effect of free radicals on [(125)I]alpha-bungarotoxin and [(3)H]epibatidine bindings. The present results further demonstrate that oxidative stress might reduce the number of [(125)I]alpha-bungarotoxin binding site and selectively suppress the expression of the nAChR subunits at protein and mRNA levels during the early stages of damage in PC12 cells.

Animals↗
PubMed2001

Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment.

The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI.

Aged↗
PubMed2001

Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications.

The neuronal nicotinic acetylcholine receptors (nAChRs) in the brain are important for functional processes, including cognitive and memory functions. The nAChRs acting as neuromodulators in communicative processes regulated by different neurotransmitters show a relatively high abundance in the human cortex, with a laminar distribution of the nAChRs of superhigh, high, and low affinity in the human cortex. The regional pattern of messenger RNA (mRNA) for various nAChR subtypes does not strictly follow the regional distribution of nAChR ligand-binding sites in the human brain. Consistent losses of nAChRs have been measured in vitro in autopsy brain tissue of Alzheimer's disease patients (AD), as well as in vivo by positron emission tomography (PET). Measurement of the protein content of nAChRs showed reduced levels of the alpha4, alpha3, and alpha7 nAChR subtypes. The finding that the alpha4 and alpha3 mRNA levels were not changed in AD brains suggests that the losses in high-affinity nicotinic-binding sites cannot be attributed to alterations at the transcriptional level of the alpha4 and alpha3 genes and that the causes have to be searched for at the translational and/or posttranslational level. The increased mRNA level of the alpha7 nAChR subtyep in the hippocampus indicates that subunit-specific changes in gene expression of the alpha7 nAChR might be associated with AD. The PET studies reveal deficits in nAChRs as an early phenomena in AD, stressing the importance of nAChRs as a potential target for drug intervention. PET ligands measuring the alpha4 nAChRs are under development. Studies of the influence of beta-amyloid on nAChRs in brain autopsy tissue from patients with the amyloid precursor protein 670/671 mutation have shown that there is no direct relationship between nAChR deficits and pathology. Treatment with cholinergic drugs in AD patients indicate improvement of the nAChRs in the brain, as visualized by PET. Further studies on neuroprotective mechanisms mediated via nAChR subtypes are exciting new avenues.

Aged↗
PubMed2001

Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells.

A line of evidence has shown that a link between the common pathological features of beta-amyloid peptide (Abeta) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to Abeta can decrease expression of nicotinic acetylcholine receptors (nAChRs), which have been shown to play roles in brain cognitive functions. Here, we report that treatment with Abeta1-40 and Abeta25-35 at nanomolar concentrations significantly decreased the [3H]epibatidine and [125I]alpha-bungarotoxin binding sites, the protein and mRNA levels of nAChR alpha3, alpha7 and beta2 subunits in PC12 cells. Abeta1-40 and Abeta25-35 at the concentrations used in the treatment study neither bound to nAChRs nor induced apoptosis, but significantly inhibited the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by Abeta may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that Abeta can degenerate nAChRs early in the course of AD before the formation of abundant Abeta fibrils.

Acetylcholine↗
PubMed2001

Nicotine-induced alterations in the expression of nicotinic receptors in primary cultures from human prenatal brain.

The nicotinic receptor proteins and gene transcripts for the different nicotinic receptor subunits exist in human prenatal brain already at 4-5 weeks of gestation. The early presence of nicotinic receptors suggests an important role for these receptors in modulating dendritic outgrowth, establishment of neuronal connections and synaptogenesis during development. When measurements of nicotinic receptors using [(3)H]epibatidine (labelling both the alpha3 and alpha4 subtype) and [(3)H]cytisine (labelling the alpha4 subtype) were performed in intact cells from the cortex, subcortical forebrain and mesencephalon (7.5-11 weeks of gestation), the highest specific binding for both ligands was detected in cells from mesencephalon, followed by subcortical forebrain and cortex. The effects of nicotine exposure were studied in primary cultures of prenatal brain (7.5-11 weeks of gestation). Treatment with nicotine (1-100 microM) for 3 days significantly increased the specific binding of [(3)H]epibatidine and [(3)H]cytisine in cortical cells but not in cells from subcortical forebrain and mesencephalon brain regions, indicating region-specific differences in the sensitivity to nicotine exposure. Relative quantification of mRNA showed that the expression of the nicotinic receptor subunits alpha3 and alpha7, but not alpha4, was increased in cortical cells after nicotine treatment. These findings support the assumption of a potential risk of disturbance in the functional role of nicotinic receptors during brain development as a consequence of maternal smoking during pregnancy.

Alkaloids↗
PubMed2001

Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia.

The laminar cortical distribution of the [125I]alpha-bungarotoxin, [3H]cytisine and [3H]epibatidine nicotinic acetylcholine receptor ligands was investigated by quantitative autoradiography in autopsy tissue from the cingulate, orbitofrontal and temporal cortices of control and schizophrenia subjects matched for age and smoking history. Different laminar binding patterns were observed for the various nicotinic ligands both in schizophrenic and control brains. [125I]alpha-Bungarotoxin binding was distributed homogeneously across all cortical layers in all three brain regions, with highest binding densities in the cingulate cortex. [3H]Cytisine and [3H]epibatidine binding varied across the cortical ribbon, with high binding in layers I, III, V and VI, within the three cortical regions. A significantly reduced [125I] alpha-bungarotoxin binding (-54%) was observed in the cingulate cortex of schizophrenia subjects, in comparison with normal individuals who smoked tobacco. In the same brain region also a significantly higher [3H]cytisine binding (48-77%) was observed in nearly all layers, except for layer I of the schizophrenia subjects, when compared to normal individuals with a history of tobacco use. No significant changes in [3H]epibatidine binding was observed within the individual cortical layers between control subjects and patients with schizophrenia, but when calculated as a whole region (i.e. measurements performed across the whole cortical ribbon), the temporal cortex showed a significant increase in [3H]epibatidine binding in schizophrenia subjects compared to control subjects. The results suggest opposite changes of the alpha4beta2 and alpha7 nicotinic receptor subtypes in the cingulate cortex of patients with schizophrenia which might reflect involvement of two different nicotinic receptor mechanisms in schizophrenia brain.

Acetylcholine↗
PubMed2001

Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Bo Söderpalm. The presentations were (1) Nicotinic mechanisms and ethanol reinforcement: Behavioral and neurochemical studies, by Bo Söderpalm, M. Ericson, P. Olausson, and J. A. Engel; (2) Chronic nicotine and ethanol: Differential regulation in gene expression of nicotinic acetylcholine receptor subunits, by X. Zhang and A. Nordberg; (3) Nicotine-ethanol interactions at neuronal nicotinic acetylcholine receptors, by Toshio Narahashi, William Marszalec, and Gary L. Aistrup; (4) Relapse prevention in alcoholics by cigarette smoking? Treatment outcome in an observational study with acamprosate, by L.G. Schmidt, U. Kalouti, M. Smolka, and M. Soyka; and (5) Effect of nicotine on voluntary ethanol intake and development of alcohol dependence in male rats, by L. Hedlund and G. Wahlström.

Acamprosate↗
PubMed2000

Preface.

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Influence of lipid peroxidation on the nicotinic acetylcholine receptors in PC12 cells.

The expression of neuronal nicotinic acetylcholine receptors (nAChRs) influenced by lipid peroxidation has been investigated. The results showed that exposure of PC12 cells to a free radical insult (FeSO(4)) induced concentration-dependent increase in level of MDA (malondialdehyde), and a significant decline in MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] reduction. In cultured cells exposed to FeSO(4), a significant dose-dependent decrease in [(3)H] epibatidine binding sites was detected and a significant reduction in B(max) value was observed in the high affinity epibatidine binding site. These results demonstrate that lipid peroxidation in cellular membranes can induce a reduction in numbers of neuronal nAChRs.

Animals↗
PubMed2000

Rats exhibiting acute behavioural tolerance to nicotine have more [125I]alpha-bungarotoxin binding sites in brain than rats not exhibiting tolerance.

Adult male Sprague-Dawley rats trained to discriminate nicotine (0.4 mg/kg, s.c. vs vehicle) using a two-lever food-reinforced operant discriminative stimulus (DS) paradigm were tested as to the ability of each subject to develop acute tolerance to nicotine. Nicotine (0.8 mg/kg, s.c.) was administered to nicotine-trained rats in their home cage and each rat tested as to its ability to detect a 2nd dose of nicotine (0.4 mg/kg, s.c.) injected at 30 min intervals thereafter (90-180 min). Tolerance was determined by evaluating nicotine-correct responding during a 2 min test session. The results of this experiment indicated that 8 out of 31 rats (26%) displayed acute tolerance (desensitizers); 18 rats (58%) did not exhibit acute tolerance (non-desensitzers) and five rats (16%) fell into a middle group and were designated as neither desensitizers or non-desensitizers. The mode time for acute tolerance was 150 min, with each desensitizer rat displaying a unique temporal profile which was replicable 4-5 weeks later. Receptor autoradiographic analysis indicated no significant differences in [3H]epibatidine binding sites in the brains of desensitizers and non-desensitizers. In contrast, [125I]alpha-bungarotoxin binding was significantly higher in a number of brain regions in desensitizers. In situ hybridization analysis revealed no difference in alpha7 nAChR subunit mRNA levels between desensitizers and non-desensitizers. These observations can be interpreted to suggest that the ability to display acute tolerance to nicotine is contingent upon the ability to upregulate alpha7 nAChRs. These data may also be central to understanding the variability of tobacco use in humans, which may be contingent on the ability of the receptors binding to alpha-bungarotoxin to be responsive to nicotine-induced desensitization.

Animals↗
PubMed2000

Development of ligands for in vivo imaging of cerebral nicotinic receptors.

Nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions. Findings from postmortem studies and clinical investigations have implicated them in the pathophysiology and treatment of Alzheimer's and Parkinson's diseases and other CNS disorders (e.g. Tourette's syndrome, epilepsy, nicotine dependence). Therefore, it ultimately might be useful to image nAChRs noninvasively for diagnosis, for studies on how changes in nAChRs might contribute to cerebral disorders, for development of therapies targeted at nAChRs, and to monitor the effects of such treatments. To date, only (S)-(-)-nicotine, radiolabeled with 11C, has been used for external imaging of nAChRs in human subjects. Since this radiotracer presents drawbacks, new ligands, with more favorable properties, have been synthesized and tested. Three general classes of compounds, namely, nicotine and its analogs, epibatidine and related compounds, and 3-pyridyl ether compounds, including A-85380, have been evaluated. Analogs of A-85380 appear to be the most promising candidates because of their low toxicity and high selectivity for the alpha4beta2 subtype of nAChRs.

Animals↗
PubMed2000

Apolipoprotein E varepsilon4 allele has an impact on vascular reactivity in Alzheimer's disease.

Seventeen otherwise healthy, non-smoking patients with probable Alzheimer's disease (AD) and 11 healthy, non-smoking, age-matched controls participated in a study of vascular reactivity. Three substances were iontophoresed into the skin: sodium nitroprusside (SNP) delivered at the cathode, and acetylcholine chloride and isoprenaline sulphate delivered at the anode. The resultant vasodilation was mapped through a laser Doppler perfusion imager. The patients harbouring the Apolipoprotein E varepsilon4 allele (ApoE4) (n=9) showed significantly greater vasodilation compared both with patients without the ApoE4 and with controls (one control possessed the ApoE4) when SNP was delivered at the cathode. An additional study of ten of the AD patients and ten controls suggested that the enhanced reactivity in the patients with the ApoE4 depended on a greater sensitivity to the iontophoretic current itself at the cathode rather than to SNP. The quotient between total cholesterol and high-density lipoprotein-cholesterol was higher in the patients with the ApoE4 compared both with patients without the ApoE4 and with controls. A dysfunction of voltage-dependent ion channels and/or other membrane abnormalities in AD patients possessing the ApoE4 is suggested.

Journal Article↗