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David Goldman - One of the best experts on this subject based on the ideXlab platform.
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interaction between childhood trauma and Serotonin Transporter gene variation in suicide
Neuropsychopharmacology, 2007Co-Authors: Xianzhang Hu, Malvin N Janal, David GoldmanAbstract:Although the Serotonin Transporter promoter polymorphism (5-HTTLPR) contributes to depression and suicidality in a fashion modulated by environmental stress, 5-HTTLPR has been little examined in relation to suicidal behavior in substance dependence. Recently, a third functional allele of 5-HTTLPR was discovered enabling more of the interindividual variation in Serotonin Transporter expression to be predicted by genotype. We examined whether the 5-HTTLPR gene alone, or interacting with childhood trauma, was predictive of suicidal behavior in substance-dependent patients, a clinical population that is at high risk of suicide, as well as childhood trauma and other stress. We interviewed 306 abstinent male African-American substance-dependent patients about whether they had ever attempted suicide and administered the 34-item Childhood Trauma Questionnaire (CTQ). Patients and 132 male African-American controls were genotyped to determine the S, LG, and LA 5-HTTLPR alleles; some analyses grouped the S and LG alleles on the basis of equivalent function. The distribution of 5-HTTLPR genotypes did not differ between patients and controls, nor between suicide attempters and non-attempters. However, patients with low expression 5-HTTLPR genotypes and above-median CTQ scores were more likely to have attempted suicide. Logistic regression showed increasing risk of a suicide attempt with increasing reports of childhood trauma scores; in addition, this increase was exaggerated among those with low expression forms of the 5-HTTLPR genotype. Childhood trauma interacts with low expressing 5-HTTLPR genotypes to increase the risk of suicidal behavior among patients with substance dependence.
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midbrain Serotonin Transporter binding potential measured with 11c dasb is affected by Serotonin Transporter genotype
Journal of Neural Transmission, 2007Co-Authors: Matthias Reimold, Michael N Smolka, Gunter Schumann, A Zimmer, Jana Wrase, Karl Mann, David Goldman, Gerald Reischl, Christoph Solbach, H J MachullaAbstract:Background. Homozygote carriers of two long (L) alleles of the Serotonin Transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [11C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of Serotonin.
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effect of a triallelic functional polymorphism of the Serotonin Transporter linked promoter region on expression of Serotonin Transporter in the human brain
American Journal of Psychiatry, 2006Co-Authors: Ramin V Parsey, Ramin S Hastings, Maria A Oquendo, Yungyu Huang, Norman R Simpson, Julie Arcement, Yiyun Huang, David Goldman, Xianzhang Hu, Todd R OgdenAbstract:OBJECTIVE: The authors examined effects of a triallelic functional polymorphism of the human Serotonin-Transporter-linked promoter region (5-HTTLPR) on in vivo expression of Serotonin Transporter in the brain in healthy volunteers and subjects with major depressive disorder. METHOD: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin Transporter binding potential (f(1)B(max)/K(d)) was determined by using positron emission tomography with the radiotracer [(11)C]McN 5652 and metabolite-corrected arterial input functions. RESULTS: There was no difference in Serotonin Transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. CONCLUSIONS: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on Serotonin Transporter binding in adulthood.
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effect of a triallelic functional polymorphism of the Serotonin Transporter linked promoter region on expression of Serotonin Transporter in the human brain
American Journal of Psychiatry, 2006Co-Authors: Ramin V Parsey, Ramin S Hastings, Maria A Oquendo, Yungyu Huang, Norman R Simpson, Julie Arcement, Yiyun Huang, Todd R Ogden, David Goldman, Ronald L Van HeertumAbstract:OBJECTIVE: The authors examined effects of a triallelic functional polymorphism of the human Serotonin-Transporter-linked promoter region (5-HTTLPR) on in vivo expression of Serotonin Transporter in the brain in healthy volunteers and subjects with major depressive disorder. METHOD: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin Transporter binding potential (f1Bmax/Kd) was determined by using positron emission tomography with the radiotracer [11C]McN 5652 and metabolite-corrected arterial input functions. RESULTS: There was no difference in Serotonin Transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. CONCLUSIONS: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to develop...
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interaction between Serotonin Transporter gene variation and rearing condition in alcohol preference and consumption in female primates
Archives of General Psychiatry, 2004Co-Authors: Christina S Barr, David Goldman, Klauspeter Lesch, Timothy K Newman, Stephen G Lindell, Courtney Shannon, Maribeth Champoux, Stephen J Suomi, Dee J HigleyAbstract:Background Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol intake and contribute to the risk for alcoholism. In humans and macaques, a promoter polymorphism that decreases transcription of the Serotonin Transporter gene is associated with anxiety and altered LHPA-axis responses to stress, and in female macaques, exposure to early-life stress alters LHPA-axis activation in response to alcohol. We wanted to determine whether Serotonin Transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence alcohol preference in female rhesus macaques. Because of the involvement of stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also wanted to determine whether Serotonin Transporter gene variation and rearing condition would influence changes in the patterns of alcohol consumption across a 6-week alcohol consumption paradigm. Methods Female macaques were reared with their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young adults, they were given access to an aspartame-sweetened 8.4% alcohol solution and vehicle for 1 hour per day, and volumes of consumption of alcoholic and nonalcoholic solutions were recorded. Serotonin Transporter genotype ( l/l and l/s ) was determined using polymerase chain reaction followed by gel electrophoresis. Results We found interactions between rearing condition and Serotonin Transporter genotype, such that l/s peer-reared females demonstrated higher levels of ethanol preference. We also found an effect of rearing condition on the percentage change in alcohol consumed during the 6 weeks as well as a phase by rearing interaction, such that peer-reared animals progressively increased their levels of consumption across the course of the study. This was especially evident for peer-reared females with the l/s rh5-HTTLPR genotype. Conclusion These data suggest a potential interaction between Serotonin Transporter gene variation and early experience in vulnerability to alcoholism.
Beth J Hoffman - One of the best experts on this subject based on the ideXlab platform.
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Serotonin Transporter messenger rna expression in neural crest derived structures and sensory pathways of the developing rat embryo
Neuroscience, 1999Co-Authors: Stefan R Hansson, Eva Mezey, Beth J HoffmanAbstract:Abstract A growing body of evidence suggests that Serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive Serotonin Transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate Serotonin Transporter messenger RNA expression during rat embryonic development. Serotonin Transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, Serotonin Transporter messenger RNA was detected in neural crest cells, some of which respond to Serotonin in vitro , and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were Serotonin Transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells, which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained Serotonin Transporter messenger RNA by late gestation. The expression of Serotonin Transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience , 83 , 1185–1201; Lebrand C. et al. (1996) Neuron , 17 , 823–835] to sensory nerves and target organs as shown in this study suggests that Serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of Serotonin Transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a Serotonin concentration gradient across epithelia, either from Serotonin in the amniotic fluid or from neuronal enteric Serotonin, as a developmental cue. Our results demonstrating Serotonin Transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the Transporter most likely responsible for the previously identified accumulation of Serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. , 8 , 265–276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development , 102 , 709–720; Shuey D. L. et al. (1992) Teratology , 46 , 367–378: Shuey D. L. et al. (1993) Anat. Embryol., Berlin , 187 , 75–85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. , 77 , 211–215; Yavarone M. S. et al. (1993) Teratology , 47 , 573–584] malformations. Serotonin Transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of Serotonin Transporter messenger RNA in early development supports the hypothesis that Serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. , 16 , 233–240], and that the morphogenctic actions of Serotonin may be regulated by transport. The striking pattern of Serotonin Transporter messenger RNA throughout developing sensory pathways suggests that Serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of Serotonin Transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of Serotonin Transporter messenger RNA during ontogeny suggests a previously unappreciated role of Serotonin in diverse physiological systems during embryonic development.
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Serotonin Transporter messenger rna expression in neural crest derived structures and sensory pathways of the developing rat embryo
Neuroscience, 1999Co-Authors: Stefan R Hansson, Eva Mezey, Beth J HoffmanAbstract:A growing body of evidence suggests that Serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive Serotonin Transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate Serotonin Transporter messenger RNA expression during rat embryonic development. Serotonin Transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, Serotonin Transporter messenger RNA was detected in neural crest cells, some of which respond to Serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were Serotonin Transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained Serotonin Transporter messenger RNA by late gestation. The expression of Serotonin Transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that Serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of Serotonin Transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a Serotonin concentration gradient across epithelia, either from Serotonin in the amniotic fluid or from neuronal enteric Serotonin, as a developmental cue. Our results demonstrating Serotonin Transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the Transporter most likely responsible for the previously identified accumulation of Serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin Transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of Serotonin Transporter messenger RNA in early development supports the hypothesis that Serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of Serotonin may be regulated by transport. The striking pattern of Serotonin Transporter messenger RNA throughout developing sensory pathways suggests that Serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of Serotonin Transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of Serotonin Transporter messenger RNA during ontogeny suggests a previously unappreciated role of Serotonin in diverse physiological systems during embryonic development.
Dennis L Murphy - One of the best experts on this subject based on the ideXlab platform.
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targeting the murine Serotonin Transporter insights into human neurobiology
Nature Reviews Neuroscience, 2008Co-Authors: Dennis L Murphy, Klauspeter LeschAbstract:Mutations resulting in reduced or completely abrogated Serotonin-Transporter (SERT) function in mice have led to the identification of more than 50 different phenotypic changes, ranging from increased anxiety and stress-related behaviours to gut dysfunction, bone weakness and late-onset obesity with metabolic syndrome. These multiple effects, which can be amplified by gene-environment and gene-gene interactions, are primarily attributable to altered intracellular and extracellular Serotonin concentrations during development and adulthood. Much of the human data relating to altered expression of the gene that encodes SERT are based on genetic-association findings or correlations and are therefore not as robust as the experimental mouse results. Nevertheless, SERT-function-modifying gene variants in humans apparently produce many phenotypes that are similar to those that manifest themselves in mice.
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are Serotonin Transporter knockout mice depressed hypoactivity but no anhedonia
Neuroreport, 2006Co-Authors: Allan V. Kalueff, Pamela S. Gallagher, Dennis L MurphyAbstract:Although the Serotonin Transporter is a key target for antidepressants, its exact role in depression etiology remains unclear. While Serotonin Transporter knockout mice are a potential model to examine this problem, their depression profile is unclear in several 'despair' tests, and may be confounded by their hypoactivity phenotype (confirmed here by marble-burying and bedding tests). To assess depression in these mice, we evaluated wild-type, heterozygous, and Serotonin Transporter knockout C57BL/6 male mice on a well-validated, anhedonia-based depression paradigm, the sucrose preference test. Overall, all three genotypes showed similar sucrose preference, indicating an unaltered hedonic state. These results demonstrate that depression-like behavior (unlike hypoactivity) is not a baseline phenotypic feature of Serotonin Transporter knockout mice, suggesting anew that these mice do not represent a genetic model of depression.
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Serotonin Transporter gene genetic disorders and pharmacogenetics
Molecular Interventions, 2004Co-Authors: Dennis L Murphy, Gary Rudnick, Alicja Lerner, Klauspeter LeschAbstract:The highly evolutionarily conserved Serotonin Transporter (SERT) regulates the entire Serotoninergic system and its receptors via modulation of extracellular fluid Serotonin concentrations. Differences in SERT expression and function produced by three SERT genes and their variants show associations with multiple human disorders. Screens of DNA from patients with autism, ADHD, bipolar disorder, and Tourette's syndrome have detected signals in the chromosome 17q region where SERT is located. Parallel investigations of SERT knockout mice have uncovered multiple phenotypes that identify SERT as a candidate gene for additional human disorders ranging from irritable bowel syndrome to obesity. Replicated studies have demonstrated that the SERT 5'-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the Serotonin reuptake inhibitors (SRIs).
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abnormal behavioral phenotypes of Serotonin Transporter knockout mice parallels with human anxiety and depression
Biological Psychiatry, 2003Co-Authors: Andrew Holmes, Dennis L Murphy, Jacqueline N CrawleyAbstract:Evidence of a link between genetic variation of the Serotonin Transporter and depression and anxiety prompted the generation of Serotonin Transporter knockout mice. Loss of Serotonin reuptake function in knock-outs causes reduced clearance of extracellular Serotonin and associated alterations in Serotonin neuronal firing and receptor function. Behavioral phenotyping function in knock-outs revealed genetic background-related abnormalities, including increased anxiety-like behaviors, reduced aggression, and exaggerated stress responses. Ongoing studies focus on identifying environmental, genetic, and developmental factors interacting with the htt mutation to produce these abnormalities. Serotonin Transporter null mutant mice provide a model system to study how genetic variation in Serotonin Transporter function affects risk for neuropsychiatric disease.
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Serotonin Transporter missense mutation associated with a complex neuropsychiatric phenotype
Molecular Psychiatry, 2003Co-Authors: Norio Ozaki, Benjamin D Greenberg, David Goldman, Walter H Kaye, K Plotnicov, J Lappalainen, Gary Rudnick, Dennis L MurphyAbstract:Two common Serotonin Transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders. We now report an uncommon coding region SERT mutation, Ile425Val, in two unrelated families with OCD and other Serotonin-related disorders. Six of the seven family members with this mutation had OCD (n=5) or obsessive-compulsive personality disorder (n=1) and some also met diagnostic criteria for multiple other disorders (Asperger's syndrome, social phobia, anorexia nervosa, tic disorder and alcohol and other substance abuse/dependence). The four most clinically affected individuals--the two probands and their two slbs--had the I425V SERT gene gain-of-function mutation and were also homozygous for 5'-UTR SERT gene variant with greater transcriptional efficacy.
Judith R Homberg - One of the best experts on this subject based on the ideXlab platform.
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knockout of the Serotonin Transporter in the rat mildly modulates decisional anhedonia
Neuroscience, 2021Co-Authors: Chao Ciugwok Guo, Michel M M Verheij, Judith R HombergAbstract:Serotonin Transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of Serotonin Transporter gene knockout (5-HTT-/-) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT-/- contributes to decisional anhedonia. To this end, we established a novel touchscreen-based go/go task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+ rats performed more optimal decision-making compared to 5-HTT-/- rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+ rats increased as the session increased in general, while 5-HTT-/- rats tended to decrease. The response time difference might indicate that 5-HTT-/- rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.
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adaptive fitness early life adversity improves adult stress coping in heterozygous Serotonin Transporter knockout rats
Molecular Psychiatry, 2013Co-Authors: R H A Van Der Doelen, Tamas Kozicz, Judith R HombergAbstract:Adaptive fitness; early life adversity improves adult stress coping in heterozygous Serotonin Transporter knockout rats
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looking on the bright side of Serotonin Transporter gene variation
Biological Psychiatry, 2011Co-Authors: Judith R Homberg, Klauspeter LeschAbstract:Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, Serotonin Transporter-linked polymorphic region (5-HTTLPR), in the human Serotonin Transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for depression in interaction with psychosocial adversity across the life span. However, genetically driven deficient Serotonin Transporter (5-HTT) function would not have been maintained throughout evolution if it only exerted negative effects without conveying any gain of function. Here, we review recent findings that humans and nonhuman primates carrying the s variant of the 5-HTTLPR outperform subjects carrying the long allele in an array of cognitive tasks and show increased social conformity. In addition, studies in 5-HTT knockout rodents are included that provide complementary insights in the beneficial effects of the 5-HTTLPR s-allele. We postulate that hypervigilance, mediated by hyperactivity in corticolimbic structures, may be the common denominator in the anxiety-related traits and (social) cognitive superiority of s-allele carriers and that environmental conditions determine whether a response will turn out to be negative (emotional) or positive (cognitive, in conformity with the social group). Taken together, these findings urge for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR variants. In fact, these factors may counterbalance or completely offset the negative consequences of the anxiety-related traits. This notion may not only explain the modest effect size of the 5-HTTLPR and inconsistent reports but may also lead to a more refined appreciation of allelic variation in 5-HTT function.
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the Serotonin Transporter knockout rat a review
Experimental Models in Serotonin Transporter Research, 2010Co-Authors: Jocelien D A Olivier, Edwin Cuppen, A R Cools, Bart A Ellenbroek, Judith R HombergAbstract:This chapter dicusses the most recent data on the Serotonin Transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the Serotonin Transporter gene, and the absence of the Serotonin Transporter has been confirmed at mRNA, protein, and functional levels. The Serotonin Transporter (SERT) plays a crucial role in Serotonin reuptake and its absence has a huge effect on Serotonin neurotransmission – exemplified by increased extracellular Serotonin levels, reduced Serotonin tissue/platelet/blood levels, and reduced evoked Serotonin release – yet the animals appear normal and do not differ from wildtype littermates in respect to breeding and health. Behavioral phenotypes are only apparent when the animals are exposed to certain stimuli. For instance, the Serotonin Transporter knock-out rat displays increased stress sensitivity in a variety of anxiety- and depression-like tests, such as the elevated plus maze test and the forced swim test. Also remarkable, while general activity is not changed, the knock-out rats show a “neurotic-like” exploratory pattern. In line with the Serotonin hypothesis of impulsivity, which argues that there is an inverse relationship between the two, Serotonin Transporter knock-out rats show reduced motor impulsivity in the five-choice serial reaction time task, and a reduction in social interaction during play and aggressive encounters. Interestingly, abdominal fat seems to be increased in the knock-out rat, despite normal body weight. Pharmacological compounds also elicit genotype-dependent responses in the knock-out rats.
Stefan R Hansson - One of the best experts on this subject based on the ideXlab platform.
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Serotonin Transporter messenger rna expression in neural crest derived structures and sensory pathways of the developing rat embryo
Neuroscience, 1999Co-Authors: Stefan R Hansson, Eva Mezey, Beth J HoffmanAbstract:Abstract A growing body of evidence suggests that Serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive Serotonin Transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate Serotonin Transporter messenger RNA expression during rat embryonic development. Serotonin Transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, Serotonin Transporter messenger RNA was detected in neural crest cells, some of which respond to Serotonin in vitro , and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were Serotonin Transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells, which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained Serotonin Transporter messenger RNA by late gestation. The expression of Serotonin Transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience , 83 , 1185–1201; Lebrand C. et al. (1996) Neuron , 17 , 823–835] to sensory nerves and target organs as shown in this study suggests that Serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of Serotonin Transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a Serotonin concentration gradient across epithelia, either from Serotonin in the amniotic fluid or from neuronal enteric Serotonin, as a developmental cue. Our results demonstrating Serotonin Transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the Transporter most likely responsible for the previously identified accumulation of Serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. , 8 , 265–276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development , 102 , 709–720; Shuey D. L. et al. (1992) Teratology , 46 , 367–378: Shuey D. L. et al. (1993) Anat. Embryol., Berlin , 187 , 75–85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. , 77 , 211–215; Yavarone M. S. et al. (1993) Teratology , 47 , 573–584] malformations. Serotonin Transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of Serotonin Transporter messenger RNA in early development supports the hypothesis that Serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. , 16 , 233–240], and that the morphogenctic actions of Serotonin may be regulated by transport. The striking pattern of Serotonin Transporter messenger RNA throughout developing sensory pathways suggests that Serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of Serotonin Transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of Serotonin Transporter messenger RNA during ontogeny suggests a previously unappreciated role of Serotonin in diverse physiological systems during embryonic development.
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Serotonin Transporter messenger rna expression in neural crest derived structures and sensory pathways of the developing rat embryo
Neuroscience, 1999Co-Authors: Stefan R Hansson, Eva Mezey, Beth J HoffmanAbstract:A growing body of evidence suggests that Serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive Serotonin Transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate Serotonin Transporter messenger RNA expression during rat embryonic development. Serotonin Transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, Serotonin Transporter messenger RNA was detected in neural crest cells, some of which respond to Serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were Serotonin Transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained Serotonin Transporter messenger RNA by late gestation. The expression of Serotonin Transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that Serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of Serotonin Transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a Serotonin concentration gradient across epithelia, either from Serotonin in the amniotic fluid or from neuronal enteric Serotonin, as a developmental cue. Our results demonstrating Serotonin Transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the Transporter most likely responsible for the previously identified accumulation of Serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin Transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of Serotonin Transporter messenger RNA in early development supports the hypothesis that Serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of Serotonin may be regulated by transport. The striking pattern of Serotonin Transporter messenger RNA throughout developing sensory pathways suggests that Serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of Serotonin Transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of Serotonin Transporter messenger RNA during ontogeny suggests a previously unappreciated role of Serotonin in diverse physiological systems during embryonic development.
