Journal of neural transmission. General section最新文献

{"title":"Characterization of [3H]clozapine binding sites in rat brain.","authors":"I Kusumi,&nbsp;S Matsubara,&nbsp;Y Takahashi,&nbsp;T Ishikane,&nbsp;T Koyama","doi":"10.1007/BF01271545","DOIUrl":"https://doi.org/10.1007/BF01271545","url":null,"abstract":"<p><p>We examined the characteristics of [3H]clozapine binding sites in four rat brain regions (frontal cortex, limbic area, hippocampus and striatum) in order to elucidate the pharmacological profile of this unique atypical antipsychotic drug. The specific [3H]clozapine binding was found to be saturable and reversible in all these brain regions. Scatchard analysis of the saturation data indicated that the specific binding consisted of high- and low-affinity components. Displacement experiments showed that the muscarinic cholinergic receptor represented about 50% of [3H]clozapine binding in each brain area. Serotonin 5-HT2 and dopamine D4 receptor binding sites could also be detected by displacement experiments using ketanserin and nemonapride, respectively, in frontal cortex and limbic area, but not in hippocampus or striatum. Alpha-1, alpha-2, histamine H1, dopamine D1, D2, or D3 receptor components could not be determined within the high-affinity [3H]clozapine binding sites in any brain region. It is possible that the atypical property of clozapine may depend on the modulatory effect on dopaminergic function via 5-HT2 receptor blockade and/or may be mediated via D4 receptor blockade in the mesocortical and mesolimbic area.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"101 1-3","pages":"51-64"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19670332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of tacrine upon murine neuroblastoma cells.","authors":"P Zatta,&nbsp;P Zambenedetti,&nbsp;M B Marturano,&nbsp;M Palumbo,&nbsp;M Nicolini","doi":"10.1007/BF01276507","DOIUrl":"https://doi.org/10.1007/BF01276507","url":null,"abstract":"<p><p>Tacrine [9-amino-1,2,3,4-tetrahydroacridine] (THA), a potent acetylcholinesterasic inhibitor, is utilized in the pharmacological treatment of Alzheimer's disease (Birne and Arie, 1994). Cytopharmacology of THA is still largely to be discovered. In the present paper we report some effects produced by THA on murine neuroblastoma cells (N2A) used as an experimental model. N2A cells treated with THA at low concentration (1 mu M) showed a reduced cell's mitosis and a remarkable reduction of protein synthesis. Eventually, a marked reduction on the phosphorylation of proteins associated to neurofilaments 200 kD, is observed using specific antibody.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"102 2","pages":"113-23"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01276507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19720927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of neuronal acetylcholine nicotinic receptor alpha 4 and beta 2 subunits during postnatal development of the rat brain.","authors":"M Cimino,&nbsp;P Marini,&nbsp;S Colombo,&nbsp;M Andena,&nbsp;F Cattabeni,&nbsp;D Fornasari,&nbsp;F Clementi","doi":"10.1007/BF01271531","DOIUrl":"https://doi.org/10.1007/BF01271531","url":null,"abstract":"<p><p>The expression of the alpha 4 and beta 2 subunits of neuronal nicotinic acetylcholine receptors (nAChRs) was studied in developing rat brain using in situ hybridization. The levels of both transcripts were already high at birth in cerebral cortex, medial habenula, CA1/CA3 regions of the hippocampus and several thalamic nuclei. In general, the beta 2 subunit showed a higher density of hybrids than the alpha 4. Beta 2 expression did not change with age in the medial habenula, medial geniculate nucleus or in the hippocampus whereas it decreased in the cortex. The developmental pattern of the hybridization signal for alpha 4 was different according to the brain area considered. The expression of the two transcripts showed a biphasic pattern in some thalamic nuclei: the lowest levels occurring during the first and second postnatal weeks respectively, and the highest levels during the second and fourth postnatal weeks. The ontogenetic profile of the expression of the alpha 4 subunit in the thalamic nuclei coincided with that of [3H]-L-nicotine binding sites. These findings suggest that the two subunits of nAChRs are independently regulated in most of the brain areas examined, and that in some regions, such as the thalamus, the ontogenetic variations reported for the alpha 4 subunit correlate with those observed for the [3H]-L-nicotine binding sites.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"100 2","pages":"77-92"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19925391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging in alcoholism: CT and MRI results and clinical correlates.","authors":"K Mann,&nbsp;G Mundle,&nbsp;M Strayle,&nbsp;P Wakat","doi":"10.1007/BF01271475","DOIUrl":"https://doi.org/10.1007/BF01271475","url":null,"abstract":"<p><p>For more than a century we have known the deleterious effects of alcohol on the brain regions surrounding the third ventricle and on the cerebellum. But it was only recently that we gained clearer evidence that the cortex is affected as well. Our imaging studies show that brain shrinkage is at least partially reversible once abstinence is maintained. They confirm results obtained in different laboratories from all over the world. Although our data contradict the rehydration hypothesis and thus lend credence to the idea of regeneration and neuroplasticity, the nature of reversibility is still a matter of debate.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"99 1-3","pages":"145-55"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19559359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency domain source localization shows state-dependent diazepam effects in 47-channel EEG.","authors":"C M Michel,&nbsp;R D Pascual-Marqui,&nbsp;W K Strik,&nbsp;T Koenig,&nbsp;D Lehmann","doi":"10.1007/BF01271476","DOIUrl":"https://doi.org/10.1007/BF01271476","url":null,"abstract":"<p><p>The topic of this study was to evaluate state-dependent effects of diazepam on the frequency characteristics of 47-channel spontaneous EEG maps. A novel method, the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study effects on the strength and the topography of the maps in the different frequency bands. Map topography was characterized by the 3-dimensional location of the equivalent dipole source and map strength was defined as the spatial standard deviation (the Global Field Power) of the maps of each frequency point. The Global Field Power can be considered as a measure of the amount of energy produced by the system, while the source location gives an estimate of the center of gravity of all sources in the brain that were active at a certain frequency. State-dependency was studied by evaluating the drug effects before and after a continuous performance task of 25 min duration. Clear interactions between drug (diazepam vs. placebo) and time after drug intake (before and after the task) were found, especially in the inferior-superior location of the dipole sources. It supports the hypothesis that diazepam, like other drugs, has different effects on brain functions depending on the momentary functional state of the brain. In addition to the drug effects, clearly different source locations and Global Field Power were found for the different frequency bands, replicating earlier reports (Michel et al., 1992).</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"99 1-3","pages":"157-71"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19559360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D2-receptor imaging with [123I]IBZM and single photon emission tomography in psychiatry: a survey of current status.","authors":"R Schlösser,&nbsp;S Schlegel","doi":"10.1007/BF01271477","DOIUrl":"https://doi.org/10.1007/BF01271477","url":null,"abstract":"<p><p>D2-dopamine receptors can be visualized in the human brain in vivo by Single Photon Emission Tomography (SPECT) and the radiolabeled benzamide [123I]IBZM. The present paper reviews the current status of this type of functional brain imaging with respect to basic methodological aspects, data analysis and quantification. The results from published clinical studies in different psychiatric patient populations and normal controls with [123I]IBZM are reviewed. [123I]IBZM-SPECT is a powerful tool for the investigation of D2-dopamine receptor status in psychiatric disorders, different types of drug treatment as well as therapeutic and side effects of pharmacologic agents. However, there still is a need for standardized imaging times and image-processing procedures. Advantages and disadvantages of SPECT with special regard to Positron Emission Tomography (PET) are also discussed.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"99 1-3","pages":"173-85"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19559361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the course of dopamine replacement therapy in patients with nocturnal myoclonus syndrome (NMS).","authors":"J Staedt,&nbsp;G Stoppe,&nbsp;A Kögler,&nbsp;H Riemann,&nbsp;G Hajak,&nbsp;D L Munz,&nbsp;D Emrich,&nbsp;E Rüther","doi":"10.1007/BF01271478","DOIUrl":"https://doi.org/10.1007/BF01271478","url":null,"abstract":"<p><p>Single photon emission tomography (SPET) permits the in vivo measurements of regional cerebral radioactivity in the human brain following the administration of compounds labeled with photon-emitting isotopes. According to our SPET findings of a reduced binding of [123I]labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) to D2 dopamine receptors in striatal structures in untreated patients with nocturnal myoclonus syndrome (NMS) it seemed to be of interest to investigate whether there are changes in D2 receptor binding under dopamine replacement therapy or not. We studied the uptake and distribution of [123I]IBZM before and in the course of dopamine replacement therapy in four patients with severe insomnia caused by a nocturnal myoclonus syndrome (NMS). We found an increase of the IBZM binding to D2 receptors in the course of treatment, which was associated with an improvement of sleep quality. Reasons for this are discussed. The [123I]IBZM SPET technique in conclusion offers an intersting tool for in vivo investigations of functional changes in the dopaminergic neurotransmitter system in longitudinal studies.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"99 1-3","pages":"187-93"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01271478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19559362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.","authors":"W Pirker,&nbsp;S Asenbaum,&nbsp;S Kasper,&nbsp;H Walter,&nbsp;P Angelberger,&nbsp;G Koch,&nbsp;A Pozzera,&nbsp;L Deecke,&nbsp;I Podreka,&nbsp;T Brücke","doi":"10.1007/BF01276462","DOIUrl":"https://doi.org/10.1007/BF01276462","url":null,"abstract":"<p><p>The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"100 3","pages":"247-56"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01276462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19721554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene.","authors":"A Heils,&nbsp;A Teufel,&nbsp;S Petri,&nbsp;M Seemann,&nbsp;D Bengel,&nbsp;U Balling,&nbsp;P Riederer,&nbsp;K P Lesch","doi":"10.1007/BF01281159","DOIUrl":"https://doi.org/10.1007/BF01281159","url":null,"abstract":"<p><p>We have isolated and characterized the 5'-flanking region and the proximal polyadenylation site of the human 5-HT transporter gene. The major gene transcript is 2,793 bp in length and it contains 208 bp of 5'-untranslated region (5'-UTR) and 694 bases of 3'-UTR. While only a single mRNA species occurs in rats and mice, the most proximal signal for polyadenylation in the human gene appears to be highly degenerate in comparison to the rat and murine motif. This polyadenylation signal-like motif may lead to alternate usage of additional polyadenylation sites resulting in multiple mRNA species in humans. A TATA-like motif and several potential binding sites for transcription factors including AP1, AP2, SP1, and a cAMP response element (CRE)-like motif are present in the 5'-flanking region. A approximately 1.7 kb fragment beginning 217 bp downstream from the transcription start site, which had been ligated into a luciferase reporter vector and transiently expressed in JAR human placental choriocarcinoma cells, displayed both constitutive and forskolin/cholera toxin-induced promoter activity. Functional promoter mapping revealed that there are negative attenuating elements between bp -1,428 and -1,185 and positive elements between bp -1,184 and -78 from the transcription initiation site. Studies with deletional mutants also indicated that core promoter sequences are contained within 78 bp of the transcription start site and that regulation of cAMP-inducible promoter activity depends on multiple cis-acting elements including two AP1 binding sites and a single CRE-like element located at bp -99. Our findings suggest that (1) the 5-HT transporter gene promoter is active in human JAR cells, but inactive in 5-HT transporter-deficient human SK-N-SH neuroblastoma and HeLa cells, (2) the information contained within 1.4 kb of 5'-flanking sequence is sufficient to confer its cell-specific expression, (3) the promoter responds to cAMP induction, and (4) the expression of the 5-HT transporter gene is regulated by a combination of positive and negative cis-acting elements operating through a basal promoter unit defined by a TATA-like motif.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"102 3","pages":"247-54"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01281159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19758883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies.","authors":"J Kornhuber,&nbsp;C G Parsons,&nbsp;S Hartmann,&nbsp;W Retz,&nbsp;S Kamolz,&nbsp;J Thome,&nbsp;P Riederer","doi":"10.1007/BF01281158","DOIUrl":"https://doi.org/10.1007/BF01281158","url":null,"abstract":"<p><p>Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.</p>","PeriodicalId":77215,"journal":{"name":"Journal of neural transmission. General section","volume":"102 3","pages":"237-46"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01281158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19758958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}