Pub Date : 2001-03-01DOI: 10.1017/S1461145701009476
H. Manji
{"title":"Strategies for Gene and Protein Expression Studies in Neuropsychopharmacology and Biological Psychiatry","authors":"H. Manji","doi":"10.1017/S1461145701009476","DOIUrl":"https://doi.org/10.1017/S1461145701009476","url":null,"abstract":"","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"83 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124116707","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002206
F. Borsini, A. Brambilla, R. Cesana, N. Grippa
This study was aimed at evaluating the ability of flibanserin, a 5-HT1A receptor full agonist with antidepressant potential, to induce the 5-HT syndrome (flat body posture, hindlimb abduction and forepaw treading) in rats previously administered with clinically active antidepressants imipramine, fluoxetine or paroxetine. The 5-HT syndrome was observed for 50 min after intraperitoneal administration of flibanserin (0, 8 or 64 mg/kg) given 10 min after antidepressants (0 or 15 mg/kg). Flibanserin induced flat body posture and very slight hindlimb abduction only at 64 mg/kg. No dose of flibanserin elicited forepaw treading. Similar but milder symptoms were induced by antidepressants. No interaction between flibanserin and antidepressants was observed. A dose of 10 mg/kg flibanserin did not change the flat body posture induced by 8 mg/kg (+/-)-8-OH-DPAT but antagonized (+/-)-8-OH-DPAT-induced forepaw treading.
{"title":"Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats.","authors":"F. Borsini, A. Brambilla, R. Cesana, N. Grippa","doi":"10.1017/S1461145701002206","DOIUrl":"https://doi.org/10.1017/S1461145701002206","url":null,"abstract":"This study was aimed at evaluating the ability of flibanserin, a 5-HT1A receptor full agonist with antidepressant potential, to induce the 5-HT syndrome (flat body posture, hindlimb abduction and forepaw treading) in rats previously administered with clinically active antidepressants imipramine, fluoxetine or paroxetine. The 5-HT syndrome was observed for 50 min after intraperitoneal administration of flibanserin (0, 8 or 64 mg/kg) given 10 min after antidepressants (0 or 15 mg/kg). Flibanserin induced flat body posture and very slight hindlimb abduction only at 64 mg/kg. No dose of flibanserin elicited forepaw treading. Similar but milder symptoms were induced by antidepressants. No interaction between flibanserin and antidepressants was observed. A dose of 10 mg/kg flibanserin did not change the flat body posture induced by 8 mg/kg (+/-)-8-OH-DPAT but antagonized (+/-)-8-OH-DPAT-induced forepaw treading.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"140 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132602258","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002188
Ivan Berlin, Robert M. Anthenelli
Although nicotine has been identified as the main ingredient in tobacco responsible for aspects of the tobacco dependence syndrome, not all of the psychopharmacological effects of smoking can be explained by nicotine alone. Accumulating preclinical and clinical evidence has demonstrated that smoking also leads to potent inhibition of both types (A and B) of monoamine oxidase (MAO). Smokers have 30-40 % lower MAOB and 20-30 % lower MAOA activity than non-smokers. Reduced MAO activity in smokers has been shown by direct measures (platelets, positron emission tomographic studies) or by indirect measures (concentration of monoamine catabolites in plasma or CSF). We examine the hypothesis that chronic habitual smoking can be better understood in the context of two pharmacological factors: nicotine and reduced MAO activity. We speculate that MAO inhibition by compounds found in either tobacco or tobacco smoke can potentiate nicotine's effects. Based on this concept, more effective anti-smoking drug strategies may be developed. As a practical consequence of tobacco smoke's MAO-inhibitory properties, comparative psychiatric research studies need to screen and control for tobacco use.
{"title":"Monoamine oxidases and tobacco smoking.","authors":"Ivan Berlin, Robert M. Anthenelli","doi":"10.1017/S1461145701002188","DOIUrl":"https://doi.org/10.1017/S1461145701002188","url":null,"abstract":"Although nicotine has been identified as the main ingredient in tobacco responsible for aspects of the tobacco dependence syndrome, not all of the psychopharmacological effects of smoking can be explained by nicotine alone. Accumulating preclinical and clinical evidence has demonstrated that smoking also leads to potent inhibition of both types (A and B) of monoamine oxidase (MAO). Smokers have 30-40 % lower MAOB and 20-30 % lower MAOA activity than non-smokers. Reduced MAO activity in smokers has been shown by direct measures (platelets, positron emission tomographic studies) or by indirect measures (concentration of monoamine catabolites in plasma or CSF). We examine the hypothesis that chronic habitual smoking can be better understood in the context of two pharmacological factors: nicotine and reduced MAO activity. We speculate that MAO inhibition by compounds found in either tobacco or tobacco smoke can potentiate nicotine's effects. Based on this concept, more effective anti-smoking drug strategies may be developed. As a practical consequence of tobacco smoke's MAO-inhibitory properties, comparative psychiatric research studies need to screen and control for tobacco use.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131873663","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}
Pub Date : 2001-03-01DOI: 10.1017/S146114570100219X
R. Pohl, V. Yeragani
Anxiety symptoms are associated with a marked increase in sudden cardiac death, suggesting an abnormality in the autonomic control of the heart. We examined the effects of sympathetic stimulation on QT interval variability in panic disorder patients by infusing the ss-adrenergic agonist isoproterenol in 6 panic disorder patients and 11 normal subjects. The ECG signal was analysed before the infusion and after 5 min after the infusion was started. The outcome measures were the QT variability normalized for mean QT interval (QTvm) and the QT variability index (QTvi), a measure of QT variability normalized by the concomitant heart rate variability. Patients with panic disorder had more variability in QT interval duration than normal controls and this variability was increased further by sympathetic stimulation with isoproterenol. The isoproterenol-associated increase in QT interval occurred in controls in the absence of significant anxiety. However, on one of two measures, the increase in QT interval variability was greater in patients with panic disorder, suggesting a greater sensitivity to isoproterenol or to isoproterenol-induced anxiety.
{"title":"QT interval variability in panic disorder patients after isoproterenol infusions.","authors":"R. Pohl, V. Yeragani","doi":"10.1017/S146114570100219X","DOIUrl":"https://doi.org/10.1017/S146114570100219X","url":null,"abstract":"Anxiety symptoms are associated with a marked increase in sudden cardiac death, suggesting an abnormality in the autonomic control of the heart. We examined the effects of sympathetic stimulation on QT interval variability in panic disorder patients by infusing the ss-adrenergic agonist isoproterenol in 6 panic disorder patients and 11 normal subjects. The ECG signal was analysed before the infusion and after 5 min after the infusion was started. The outcome measures were the QT variability normalized for mean QT interval (QTvm) and the QT variability index (QTvi), a measure of QT variability normalized by the concomitant heart rate variability. Patients with panic disorder had more variability in QT interval duration than normal controls and this variability was increased further by sympathetic stimulation with isoproterenol. The isoproterenol-associated increase in QT interval occurred in controls in the absence of significant anxiety. However, on one of two measures, the increase in QT interval variability was greater in patients with panic disorder, suggesting a greater sensitivity to isoproterenol or to isoproterenol-induced anxiety.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114961887","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002267
C. Rohlff
Assessing human cerebrospinal fluid (CSF) provides a practical way to conduct longitudinal molecular analyses of changes during the course of neurological disease. Integrated and parallel analyses of neurotransmitters, neuropeptides and proteins in CSF may reveal better insights into complex interaction of numerous cell types in the central nervous system (CNS) at an unprecedented level of complexity and detail. Intricate molecular fingerprints of CSF proteins may pinpoint multiple underlying pathogenic mechanisms as well as an acute and a chronic CNS disease component. Some of these changes may be mapped to altered protein expression patterns in clinically relevant cell populations with a causative or diagnostic disease link. A CNS proteome database of primary human CNS tissues may avoid ambiguities of experimental models and accelerate pre- and clinical development of more specific diagnostic and prognostic disease markers and new selective therapeutics.
{"title":"Proteomics in neuropsychiatric disorders.","authors":"C. Rohlff","doi":"10.1017/S1461145701002267","DOIUrl":"https://doi.org/10.1017/S1461145701002267","url":null,"abstract":"Assessing human cerebrospinal fluid (CSF) provides a practical way to conduct longitudinal molecular analyses of changes during the course of neurological disease. Integrated and parallel analyses of neurotransmitters, neuropeptides and proteins in CSF may reveal better insights into complex interaction of numerous cell types in the central nervous system (CNS) at an unprecedented level of complexity and detail. Intricate molecular fingerprints of CSF proteins may pinpoint multiple underlying pathogenic mechanisms as well as an acute and a chronic CNS disease component. Some of these changes may be mapped to altered protein expression patterns in clinically relevant cell populations with a causative or diagnostic disease link. A CNS proteome database of primary human CNS tissues may avoid ambiguities of experimental models and accelerate pre- and clinical development of more specific diagnostic and prognostic disease markers and new selective therapeutics.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"74 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123629887","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002243
M. Strakhova, P. Skolnick
The past decade has been marked by a dramatic increase in the availability of techniques to identify and clone genes that are differentially expressed in disease states and by drug treatments. The applications of such techniques to problems in biological psychiatry are manifold and the implications of discovering novel and/or known genes that are perturbed in neuropsychiatric disorders profound. While there are success stories, it is becoming ever more apparent that each of these techniques has its limitations, particularly when applied to the central nervous system. Given that these methods (e.g. differential display, RNA fingerprinting, suppression-subtractive hybridization, microarrays) are labour-intensive and potentially time-consuming, it is important to understand these limitations. For example, differential display is capable of detecting very small changes in the expression of mRNA species. Methods like suppression-subtractive hybridization are better suited to examine potential differences in rare transcripts, but only when their expression is changed substantially (currently ? 5-fold). Moreover, both the functional and morphological organization of the central nervous system present challenges that may not be encountered in other systems. In this overview, we will discuss the advantages and disadvantages of some of these approaches and their application to research in biological psychiatry.
{"title":"Can 'differential display' methodologies make an impact on biological psychiatry?","authors":"M. Strakhova, P. Skolnick","doi":"10.1017/S1461145701002243","DOIUrl":"https://doi.org/10.1017/S1461145701002243","url":null,"abstract":"The past decade has been marked by a dramatic increase in the availability of techniques to identify and clone genes that are differentially expressed in disease states and by drug treatments. The applications of such techniques to problems in biological psychiatry are manifold and the implications of discovering novel and/or known genes that are perturbed in neuropsychiatric disorders profound. While there are success stories, it is becoming ever more apparent that each of these techniques has its limitations, particularly when applied to the central nervous system. Given that these methods (e.g. differential display, RNA fingerprinting, suppression-subtractive hybridization, microarrays) are labour-intensive and potentially time-consuming, it is important to understand these limitations. For example, differential display is capable of detecting very small changes in the expression of mRNA species. Methods like suppression-subtractive hybridization are better suited to examine potential differences in rare transcripts, but only when their expression is changed substantially (currently ? 5-fold). Moreover, both the functional and morphological organization of the central nervous system present challenges that may not be encountered in other systems. In this overview, we will discuss the advantages and disadvantages of some of these approaches and their application to research in biological psychiatry.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"137 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115791304","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002218
R. McAllister-Williams, Amanda J. Anderson, Allan H. Young
The 5-HT1A agonist 8-OH-DPAT produces a hypothermia in mice mediated by somatodendritic 5-HT1A receptors, that is attenuated by antidepressants and corticosterone. The present study investigated if the effect of corticosterone is specific to the serotonergic system or a non-specific effect on thermoregulation. Administration of corticosterone for 3 d had no effect on dopaminergic (apomorphine) or adrenergic (clonidine) hypothermic challenges. However in addition to 8-OH-DPAT, nicotine-induced hypothermia was attenuated by corticosterone. Administration of the selective nicotinic antagonist mecamylamine had no effect on 8-OH-DPAT-induced hypothermia, although nicotine-induced hypothermia was attenuated by the selective 5-HT1A antagonist WAY-100635. This demonstrates a serotonergic-nicotinic interaction in the generation of hypothermia in mice and is consistent with corticosterone selectively attenuating somatodendritic 5-HT1A receptor function.
{"title":"Corticosterone selectively attenuates 8-OH-DPAT-mediated hypothermia in mice.","authors":"R. McAllister-Williams, Amanda J. Anderson, Allan H. Young","doi":"10.1017/S1461145701002218","DOIUrl":"https://doi.org/10.1017/S1461145701002218","url":null,"abstract":"The 5-HT1A agonist 8-OH-DPAT produces a hypothermia in mice mediated by somatodendritic 5-HT1A receptors, that is attenuated by antidepressants and corticosterone. The present study investigated if the effect of corticosterone is specific to the serotonergic system or a non-specific effect on thermoregulation. Administration of corticosterone for 3 d had no effect on dopaminergic (apomorphine) or adrenergic (clonidine) hypothermic challenges. However in addition to 8-OH-DPAT, nicotine-induced hypothermia was attenuated by corticosterone. Administration of the selective nicotinic antagonist mecamylamine had no effect on 8-OH-DPAT-induced hypothermia, although nicotine-induced hypothermia was attenuated by the selective 5-HT1A antagonist WAY-100635. This demonstrates a serotonergic-nicotinic interaction in the generation of hypothermia in mice and is consistent with corticosterone selectively attenuating somatodendritic 5-HT1A receptor function.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133701014","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002255
N. Johnston-Wilson, Christopher M. L. S. Bouton, Jonathan Pevsner, Joseph J. Breen, E. Torrey, R. Yolken
Neuropsychiatric diseases such as schizophrenia and bipolar disorder are major causes of morbidity throughout the world. Despite extensive searches, no single gene, RNA transcript, or protein has been found which can, on its own, account for these disorders. Recently, the availability of genomic tools such as cDNA microarrays, serial analysis of gene expression (SAGE) and large-scale sequencing of cDNA libraries has allowed researchers to assay biological samples for a large number of RNA transcripts. Similarly, proteomic tools allow for the quantitation of a large number of peptides and proteins. These methods include two-dimensional electrophoresis and surface-enhanced laser desorption/ionization (SELDI). We have initiated experiments which apply these techniques to the comparison of RNAs and proteins expressed in clinical samples obtained from individuals with psychiatric diseases and controls. These methods have the potential to identify pathways that are involved in the pathogenesis of complex psychiatric disorders. The characterization of these pathways may allow for the development of new methods for the diagnosis and treatment of schizophrenia, bipolar disorder, and other human psychiatric diseases.
{"title":"Emerging technologies for large-scale screening of human tissues and fluids in the study of severe psychiatric disease.","authors":"N. Johnston-Wilson, Christopher M. L. S. Bouton, Jonathan Pevsner, Joseph J. Breen, E. Torrey, R. Yolken","doi":"10.1017/S1461145701002255","DOIUrl":"https://doi.org/10.1017/S1461145701002255","url":null,"abstract":"Neuropsychiatric diseases such as schizophrenia and bipolar disorder are major causes of morbidity throughout the world. Despite extensive searches, no single gene, RNA transcript, or protein has been found which can, on its own, account for these disorders. Recently, the availability of genomic tools such as cDNA microarrays, serial analysis of gene expression (SAGE) and large-scale sequencing of cDNA libraries has allowed researchers to assay biological samples for a large number of RNA transcripts. Similarly, proteomic tools allow for the quantitation of a large number of peptides and proteins. These methods include two-dimensional electrophoresis and surface-enhanced laser desorption/ionization (SELDI). We have initiated experiments which apply these techniques to the comparison of RNAs and proteins expressed in clinical samples obtained from individuals with psychiatric diseases and controls. These methods have the potential to identify pathways that are involved in the pathogenesis of complex psychiatric disorders. The characterization of these pathways may allow for the development of new methods for the diagnosis and treatment of schizophrenia, bipolar disorder, and other human psychiatric diseases.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125062635","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002164
G. Becker, D. Berg, K. Lesch, T. Becker
The pathogenesis of major depression (MD) remains unclear despite intensive research in the last decades which brought up a multitude of findings illustrating the complexity of this disorder. In this paper we will summarize the evidence pointing towards a structural alteration of the basal limbic system in MD and depression in Parkinson's disease (PD). Transcranial ultrasound and MRI studies in both depressive syndromes revealed altered signal intensity of the brainstem midline comprising fibre tracts of the basal limbic system. The hypothesis of a structural disruption of the basal limbic system is supported by biochemical and histopathological findings. The similarity of findings in MD and depression in PD might reflect a relationship between MD and neurodegenerative disorders.
{"title":"Basal limbic system alteration in major depression: a hypothesis supported by transcranial sonography and MRI findings.","authors":"G. Becker, D. Berg, K. Lesch, T. Becker","doi":"10.1017/S1461145701002164","DOIUrl":"https://doi.org/10.1017/S1461145701002164","url":null,"abstract":"The pathogenesis of major depression (MD) remains unclear despite intensive research in the last decades which brought up a multitude of findings illustrating the complexity of this disorder. In this paper we will summarize the evidence pointing towards a structural alteration of the basal limbic system in MD and depression in Parkinson's disease (PD). Transcranial ultrasound and MRI studies in both depressive syndromes revealed altered signal intensity of the brainstem midline comprising fibre tracts of the basal limbic system. The hypothesis of a structural disruption of the basal limbic system is supported by biochemical and histopathological findings. The similarity of findings in MD and depression in PD might reflect a relationship between MD and neurodegenerative disorders.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"276 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123304048","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}
Pub Date : 2001-03-01DOI: 10.1017/S1461145701002231
Jun-feng Wang, C. Bown, Biao Chen, L. Young
An increasing body of evidence demonstrates that lithium and valproate have a regulatory effect on signal transduction pathways. Alteration of signalling molecules triggers changes in gene expression which are thought to contribute to the therapeutic effects of these drugs on bipolar disorder. Differential-display PCR was used to identify genes in rat cerebral cortex that are regulated by chronic treatment with lithium and valproate. One novel lithium-regulated gene was identified and was characterized and studied further with 5'-RACE-PCR and library screening. We also found that valproate regulated the expression of the 78-kDa glucose-regulated protein (GRP78). Chronic treatment with valproate has also been found to increase gene transcription, mRNA and protein levels of GRP78. These results suggest novel targets for lithium and valproate that may be relevant to their mechanism of action. The data further our understanding of the mechanism of the action of mood stabilizers, and help identify new targets for genetic studies and therapeutic strategies in bipolar disorder.
{"title":"Identification of mood stabilizer-regulated genes by differential-display PCR.","authors":"Jun-feng Wang, C. Bown, Biao Chen, L. Young","doi":"10.1017/S1461145701002231","DOIUrl":"https://doi.org/10.1017/S1461145701002231","url":null,"abstract":"An increasing body of evidence demonstrates that lithium and valproate have a regulatory effect on signal transduction pathways. Alteration of signalling molecules triggers changes in gene expression which are thought to contribute to the therapeutic effects of these drugs on bipolar disorder. Differential-display PCR was used to identify genes in rat cerebral cortex that are regulated by chronic treatment with lithium and valproate. One novel lithium-regulated gene was identified and was characterized and studied further with 5'-RACE-PCR and library screening. We also found that valproate regulated the expression of the 78-kDa glucose-regulated protein (GRP78). Chronic treatment with valproate has also been found to increase gene transcription, mRNA and protein levels of GRP78. These results suggest novel targets for lithium and valproate that may be relevant to their mechanism of action. The data further our understanding of the mechanism of the action of mood stabilizers, and help identify new targets for genetic studies and therapeutic strategies in bipolar disorder.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125496369","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：