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9 - Modeling SERT × BDNF interactions in brain disorders: single BDNF gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities in serotonin transporter knock-out mice

Published online by Cambridge University Press:  06 July 2010

By
Justin L. Laporte ,
Renee F. Ren-Patterson ,
Dennis L. Murphy  and
Allan V. Kalueff
Edited by
Allan V. Kalueff  and
Justin L. LaPorte
Allan V. Kalueff
Affiliation:
Georgetown University Medical Center
Justin L. LaPorte
Affiliation:
National Institute of Mental Health
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Summary

ABSTRACT

There is growing clinical evidence that many psychiatric illnesses have overlapping genetic mechanisms. Understanding these mechanisms is important to the improvement of psychiatric treatment and preventions of the disorders, and animal genetic models continue to be a critical avenue of research towards these ends. As serotonin is a key neurotransmitter with important roles in normal behavioral processes and has been implicated in the pathogenesis of psychopathological conditions such as depression, anxiety, and addiction, it is a prime target for investigation in behavioral neurogenetics. The serotonin transporter (SERT) is a key brain protein that regulates the amount of serotonin that can activate the receptor. It is becoming evident that SERT interacts with brain-derived neurotrophic factor (BDNF), an important modulator of dopaminergic, cholinergic, and serotonergic neurons, which has been linked to memory function, activity, eating behavior, depression, and anxiety. The pivotal roles played by these two brain molecules have resulted in the development of numerous mutant animal models that have reduced function of SERT, BDNF, or both. Interestingly, SERT × BDNF mutant mice show numerous different behavioral phenotypes that are distinct from either SERT mutants or BDNF mutants alone, displaying phenotypes that are highly relevant to human clinical scenarios and bringing them added validity. This chapter will provide data from numerous experiments utilizing these rodent models and will explain their relevance and validity for research into the genetics of neuropsychiatric disorders.

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Experimental Models in Serotonin Transporter Research , pp. 270 - 287
Publisher: Cambridge University Press
Print publication year: 2010

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References

Adayev, T, Ranasinghe, B, Banerjee, P (2005). Transmembrane signaling in the brain by serotonin, a key regulator of physiology and emotion. Bioscience Reports 25: 363–85.CrossRefGoogle ScholarPubMed
Aghajanian, G K (1990). Serotonin-induced inward current in rat facial motoneurons: evidence for mediation by G proteins but not protein kinase C. Brain Res 524: 171–4.CrossRefGoogle Scholar
Aghajanian, G K, Marek, G J (1997). Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36: 589–99.CrossRefGoogle ScholarPubMed
Aghajanian, G K, Marek, G J (1999). Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res 825: 161–71.CrossRefGoogle Scholar
Aloe, L, Iannitelli, A, Angelucci, F, Bersani, G, Fiore, M (2000). Studies in animal models and humans suggesting a role of nerve growth factor in schizophrenia-like disorders. Behav Pharmacol 11: 235–42.CrossRefGoogle ScholarPubMed
Angelucci, F, Aloe, L, Vasquez, P J, Mathe, A A (2000). Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression. Neuroreport 11: 1369–73.CrossRefGoogle Scholar
Angelucci, F, Brene, S, Mathe, A A (2005). BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 10: 345–52.CrossRefGoogle ScholarPubMed
Angelucci, F, Mathe, A A, Aloe, L (2004). Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia. Progr Brain Res 146: 151–65.CrossRefGoogle Scholar
Ansorge, M S, Zhou, M, Lira, A, Hen, R, Gingrich, J A (2004). Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306: 879–81.CrossRefGoogle ScholarPubMed
Bartoletti, A, Cancedda, L, Reid, S W, et al. (2002). Heterozygous knock-out mice for brain-derived neurotrophic factor show a pathway-specific impairment of long-term potentiation but normal critical period for monocular deprivation. J Neurosci 22: 10 072–7.CrossRefGoogle ScholarPubMed
Berton, O, McClung, C A, Dileone, R J, et al. (2006). Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311: 864–8.CrossRefGoogle ScholarPubMed
Bjorntorp, P (2001). Do stress reactions cause abdominal obesity and comorbidities?Obes Rev 2: 73–86.CrossRefGoogle ScholarPubMed
Bjorntorp, P, Rosmond, R (2000). Obesity and cortisol. Nutrition Burbank, Los Angeles County, Calif 16: 924–36.CrossRefGoogle ScholarPubMed
Bonhoeffer, T (1996). Neurotrophins and activity-dependent development of the neocortex. Curr Opin Neurobiol 6: 119–26.CrossRefGoogle ScholarPubMed
Bonnin, A, Peng, W, Hewlett, W, Levitt, P (2006). Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience 141: 781–94.CrossRefGoogle ScholarPubMed
Bonnin, A, Torii, M, Wang, L, Rakic, P, Levitt, P (2007). Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci 10: 588–97.CrossRefGoogle ScholarPubMed
Chourbaji, S, Hellweg, R, Brandis, D, et al. (2004). Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Brain Res Mol Brain Res 121: 28–36.CrossRefGoogle ScholarPubMed
Crawley, J N (1999). Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res 835: 18–26.CrossRefGoogle ScholarPubMed
Dutton, M A, Lee, E W, Zukowska, Z (2006). NPY and extreme stress: lessons learned from posttraumatic stress disorder. Exs: 213–22.Google ScholarPubMed
Eaton, M J, Whittemore, S R (1996). Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells grafted into the adult rat CNS. Exp Neurol 140: 105–14.CrossRefGoogle ScholarPubMed
Egan, M F, Kojima, M, Callicott, J H, et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112: 257–69.CrossRefGoogle ScholarPubMed
Firk, C, Markus, C R (2007). Review: Serotonin by stress interaction: a susceptibility factor for the development of depression?J Psychopharmacol 21: 538–44.CrossRefGoogle Scholar
Galter, D, Unsicker, K (2000a). Brain-derived neurotrophic factor and TrkB are essential for cAMP-mediated induction of the serotonergic neuronal phenotype. J Neurosci Res 61: 295–301.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Galter, D, Unsicker, K (2000b). Sequential activation of the 5-HT1(A) serotonin receptor and TrkB induces the serotonergic neuronal phenotype. Mol Cell Neurosci 15: 446–55.CrossRefGoogle ScholarPubMed
Garoflos, E, Panagiotaropoulos, T, Pondiki, S, Stamatakis, A, Philippidis, E, Stylianopoulou, F (2005). Cellular mechanisms underlying the effects of an early experience on cognitive abilities and affective states. Ann Gen Psychiatry 4: 8.CrossRefGoogle ScholarPubMed
Glatt, C E, DeYoung, J A, Delgado, S, et al. (2001). Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Nat Genet 27: 435–8.CrossRefGoogle ScholarPubMed
Glatt, C E, Reus, V I (2003). Pharmacogenetics of monoamine transporters. Pharmacogenomics 4: 583–96.CrossRefGoogle ScholarPubMed
Graeff, F G, Guimaraes, F S, Andrade, T G, Deakin, J F (1996). Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54: 129–41.CrossRefGoogle Scholar
Gross, C, Hen, R (2004a). The developmental origins of anxiety. Nature Rev 5: 545–52.CrossRefGoogle ScholarPubMed
Gross, C, Hen, R (2004b). Genetic and environmental factors interact to influence anxiety. Neurotox Res 6: 493–501.CrossRefGoogle ScholarPubMed
Gross, C, Santarelli, L, Brunner, D, Zhuang, X, Hen, R (2000). Altered fear circuits in 5-HT(1A) receptor KO mice. Biol Psychiatry 48: 1157–63.CrossRefGoogle ScholarPubMed
Gross, C, Zhuang, X, Stark, K, et al. (2002). Serotonin1A receptor acts during development to establish normal anxiety-like behavior in the adult. Nature 416: 396–400.CrossRefGoogle ScholarPubMed
Hall, D, Dhilla, A, Charalambous, A, Gogos, J A, Karayiorgou, M (2003). Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Human Genet 73: 370–6.CrossRefGoogle ScholarPubMed
Hariri, A R, Holmes, A (2006). Genetics of emotional regulation: the role of the serotonin transporter in neural function. Trends Cogn Sci 10: 182–91.CrossRefGoogle ScholarPubMed
Holmes, A, Hariri, A R (2003). The serotonin transporter gene-linked polymorphism and negative emotionality: placing single gene effects in the context of genetic background and environment. Genes Brain Behav 2: 332–5.CrossRefGoogle Scholar
Kaiser, A, Fedrowitz, M, Ebert, U, et al. (2001). Auditory and vestibular defects in the circling (ci2) rat mutant. Eur J Neurosci 14: 1129–42.CrossRefGoogle ScholarPubMed
Kalueff, A, Nutt, D J (1996). Role of GABA in memory and anxiety. Depress Anxiety 4: 100–10.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Kalueff, A V, Ren-Patterson, R F, Murphy, D L (2007a). The developing use of heterozygous mutant mouse models in brain monoamine transporter research. Trends Pharmacol Sci 28: 122–7.CrossRefGoogle ScholarPubMed
Kalueff, A V, Tuohimaa, P (2004). Experimental modeling of anxiety and depression. Acta Neurobiol Exp (Wars) 64: 439–48.Google ScholarPubMed
Kalueff, A V, Wheaton, M, Murphy, D L (2007b). What's wrong with my mouse model? Advances and strategies in animal modeling of anxiety and depression. Behav Brain Res 179: 1–18.CrossRefGoogle ScholarPubMed
Karege, F, Perret, G, Bondolfi, G, Schwald, M, Bertschy, G, Aubry, J M (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109: 143–8.CrossRefGoogle ScholarPubMed
Kaufman, J, Yang, B Z, Douglas-Palumberi, H, et al. (2006). Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry 59: 673–80.CrossRefGoogle ScholarPubMed
Kennedy, J L, Farrer, L A, Andreasen, N C, Mayeux, R, St George-Hyslop, P (2003). The genetics of adult-onset neuropsychiatric disease: complexities and conundra?Science 302: 822–6.CrossRefGoogle ScholarPubMed
Kernie, S G, Liebl, D J, Parada, L F (2000). BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19: 1290–300.CrossRefGoogle ScholarPubMed
Kim, J M, Stewart, R, Kim, S W, et al. (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biol Psychiatry 62: 423–8.CrossRefGoogle ScholarPubMed
Kuipers, S D, Bramham, C R (2006). Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Current Opini Drug Discov Dev 9: 580–6.Google ScholarPubMed
Kuo, L E, Abe, K, Zukowska, Z (2007a). Stress, NPY and vascular remodeling: implications for stress-related diseases. Peptides 28: 435–40.CrossRefGoogle ScholarPubMed
Kuo, L E, Kitlinska, J B, Tilan, J U, et al. (2007b). Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nature Med 13: 803–11.CrossRefGoogle ScholarPubMed
Lauder, J M (1990). Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal. Ann NY Acad Sci 600: 297–313; discussion 314.CrossRefGoogle ScholarPubMed
Lesch, K P (2005a). Genetic alterations of the murine serotonergic gene pathway: the neurodevelopmental basis of anxiety. Handb Exp Pharmacol 169: 71–112.CrossRefGoogle Scholar
Lesch, K P (2005b). Serotonergic gene inactivation in mice: models for anxiety and aggression?Novartis Found Symp 268: 111–40; discussion 140–6, 167–70.Google ScholarPubMed
Lesch, K P, Mossner, R (2006). Inactivation of 5HT transport in mice: modeling altered 5HT homeostasis implicated in emotional dysfunction, affective disorders, and somatic syndromes. Handb Exp Pharmacol 175: 417–56.CrossRefGoogle Scholar
Lesch, K P, Zeng, Y, Reif, A, Gutknecht, L (2003). Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol 480: 185–204.CrossRefGoogle ScholarPubMed
Licinio, J, Wong, M L (2002). Brain-derived neurotrophic factor (BDNF) in stress and affective disorders. Mol Psychiatry 7: 519.CrossRefGoogle ScholarPubMed
Lohoff, F W, Sander, T, Ferraro, T N, Dahl, J P, Gallinat, J, Berrettini, W H (2005). Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet 139: 51–3.CrossRefGoogle Scholar
Lucki, I (1998). The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44: 151–62.CrossRefGoogle ScholarPubMed
Lyons, W E, Mamounas, L A, Ricaurte, G A, et al. (1999). Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 96: 15 239–44.CrossRefGoogle ScholarPubMed
Mamounas, L A, Altar, C A, Blue, M E, Kaplan, D R, Tessarollo, L, Lyons, W E (2000). BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain. J Neurosci 20: 771–82.CrossRefGoogle Scholar
Mamounas, L A, Blue, M E, Siuciak, J A, Altar, C A (1995). Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 15: 7929–39.CrossRefGoogle ScholarPubMed
Martinowich, K, Lu, B (2008). Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 33: 73–83.CrossRefGoogle ScholarPubMed
Martinowich, K, Manji, H, Lu, B (2007). New insights into BDNF function in depression and anxiety. Nat Neurosci 10: 1089–93.CrossRefGoogle ScholarPubMed
McAllister, A K (1999). Subplate neurons: a missing link among neurotrophins, activity, and ocular dominance plasticity?Proc Natl Acad Sci USA 96: 13 600–02.CrossRefGoogle ScholarPubMed
Meyer, J H (2007). Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32: 86–102.Google ScholarPubMed
Minichiello, L, Korte, M, Wolfer, D, et al. (1999). Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24: 401–14.CrossRefGoogle ScholarPubMed
Mossner, R, Daniel, S, Albert, D, et al. (2000). Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36: 197–202.CrossRefGoogle Scholar
Murphy, D L, Lerner, A, Rudnick, G, Lesch, K P (2004). Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 4: 109–23.CrossRefGoogle ScholarPubMed
Murphy, D L, Li, Q, Engel, S, et al. (2001). Genetic perspectives on the serotonin transporter. Brain Res Bull 56: 487–94.CrossRefGoogle ScholarPubMed
Murphy, D L, Uhl, G R, Holmes, A, et al. (2003). Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders. Genes Brain Behav 2: 350–64.CrossRefGoogle ScholarPubMed
Nestler, E J, Barrot, M, DiLeone, R J, Eisch, A J, Gold, S J, Monteggia, L M (2002). Neurobiology of depression. Neuron 34: 13–25.CrossRefGoogle Scholar
Neves-Pereira, M, Cheung, J K, Pasdar, A, et al. (2005). BDNF gene is a risk factor for schizophrenia in a Scottish population. Mol Psychiatry 10: 208–12.CrossRefGoogle Scholar
Owens, M J, Nemeroff, C B (1994). Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 40: 288–95.Google ScholarPubMed
Ozaki, N, Goldman, D, Kaye, W H, et al. (2003). Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 8: 933–6.CrossRefGoogle ScholarPubMed
Panagiotaropoulos, T, Papaioannou, A, Pondiki, S, Prokopiou, A, Stylianopoulou, F, Gerozissis, K (2004). Effect of neonatal handling and sex on basal and chronic stress-induced corticosterone and leptin secretion. Neuroendocrinology 79: 109–18.CrossRefGoogle ScholarPubMed
Pozzo-Miller, L D, Gottschalk, W, Zhang, L, et al. (1999). Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice. J Neurosci 19: 4972–83.CrossRefGoogle ScholarPubMed
Ren-Patterson, R F, Cochran, L W, Holmes, A, Lesch, K P, Lu, B, Murphy, D L (2006). Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies. Cell Mol Neurobiol 26: 755–80.CrossRefGoogle ScholarPubMed
Ren-Patterson, R F, Cochran, L W, Holmes, A, et al. (2005a). Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice. J Neurosci Res 79: 756–71.CrossRefGoogle ScholarPubMed
Ren-Patterson, R F, Kim, D K, Zheng, X, et al. (2005b). Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT. Faseb J 19: 1537–9.CrossRefGoogle ScholarPubMed
Rosmond, R, Dallman, M F, Bjorntorp, P (1998). Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 83: 1853–9.Google ScholarPubMed
Rudnick, G (2006a). Serotonin transporters – structure and function. J Membr Biol 213: 101–10.CrossRefGoogle ScholarPubMed
Rudnick, G (2006b). Structure/function relationships in serotonin transporter: new insights from the structure of a bacterial transporter. Handb Exp Pharmacol 175: 59–73.CrossRefGoogle Scholar
Rumajogee, P, Madeira, A, Verge, D, Hamon, M, Miquel, M C (2002). Up-regulation of the neuronal serotoninergic phenotype in vitro: BDNF and cAMP share TrkB-dependent mechanisms. J Neurochem 83: 1525–8.CrossRefGoogle Scholar
Rumajogee, P, Verge, D, Darmon, M, Brisorgueil, M J, Hamon, M, Miquel, M C (2005). Rapid up-regulation of the neuronal serotoninergic phenotype by brain-derived neurotrophic factor and cyclic adenosine monophosphate: relations with raphe astrocytes. J Neurosci Res 81: 481–7.CrossRefGoogle ScholarPubMed
Rumajogee, P, Verge, D, Hamon, M, Miquel, M C (2006). Somato-dendritic distribution of 5-HT(1A) and 5-HT(1B) autoreceptors in the BDNF- and cAMP-differentiated RN46A serotoninergic raphe cell line. Brain Res 1085: 121–6.CrossRefGoogle ScholarPubMed
Rumajogee, P, Verge, D, Hanoun, N, et al. (2004). Adaption of the serotoninergic neuronal phenotype in the absence of 5-HT autoreceptors or the 5-HT transporter: involvement of BDNF and cAMP. Eur J Neurosci 19: 937–44.CrossRefGoogle ScholarPubMed
Senkowski, D, Linden, M, Zubragel, D, Bar, T, Gallinat, J (2003). Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder. Biol Psychiatry 53: 304–14.CrossRefGoogle ScholarPubMed
Shiah, I S, Yatham, L N (2000). Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies. Bipolar Disord 2: 77–92.CrossRefGoogle ScholarPubMed
Sklar, P, Gabriel, S B, McInnis, M G, et al. (2002). Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry 7: 579–93.CrossRefGoogle ScholarPubMed
Solano, J M, Jacobson, L (1999). Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA. Am J Physiol 277: E708–16.Google ScholarPubMed
Tjurmina, O A, Armando, I, Saavedra, J M, Goldstein, D S, Murphy, D L (2002). Exaggerated adrenomedullary response to immobilization in mice with targeted disruption of the serotonin transporter gene. Endocrinology 143: 4520–6.CrossRefGoogle ScholarPubMed
Tonra, J R, Ono, M, Liu, X, et al. (1999). Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice. Diabetes 48: 588–94.CrossRefGoogle ScholarPubMed
Turlejski, K (1996). Evolutionary ancient roles of serotonin: long-lasting regulation of activity and development. Acta Neurobiol Exp (Wars) 56: 619–36.Google ScholarPubMed
Meer, P, Raber, J (2005). Mouse behavioral analysis in systems biology. Biochem J 389: 593–610.Google ScholarPubMed
Vetter, D E, Li, C, Zhao, L, et al. (2002). Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior. Nat Genet 31: 363–9.CrossRefGoogle ScholarPubMed
Vitalis, T, Cases, O, Gillies, K, et al. (2002). Interactions between TrkB signaling and serotonin excess in the developing murine somatosensory cortex: a role in tangential and radial organization of thalamocortical axons. J Neurosci 22: 4987–5000.CrossRefGoogle ScholarPubMed
Vitalis, T, Cases, O, Passemard, S, Callebert, J, Parnavelas, J G (2007). Embryonic depletion of serotonin affects cortical development. Eur J Neurosci 26: 331–44.CrossRefGoogle ScholarPubMed
Vitalis, T, Parnavelas, J G (2003). The role of serotonin in early cortical development. Dev Neurosci 25: 245–56.CrossRefGoogle ScholarPubMed
Whitaker-Azmitia, P M (1991). Role of serotonin and other neurotransmitter receptors in brain development: basis for developmental pharmacology. Pharmacol Rev 43: 553–61.Google ScholarPubMed
Whitaker-Azmitia, P M (1999). The discovery of serotonin and its role in neuroscience. Neuropsychopharmacology 21: 2S–8S.CrossRefGoogle ScholarPubMed
Whitaker-Azmitia, P M (2001). Serotonin and brain development: role in human developmental diseases. Brain Res Bull 56: 479–85.CrossRefGoogle ScholarPubMed
Whitaker-Azmitia, P M, Druse, M, Walker, P, Lauder, J M (1996). Serotonin as a developmental signal. Behav Brain Res 73: 19–29.CrossRefGoogle ScholarPubMed
Xu, B, Zang, K, Ruff, N L, et al. (2000). Cortical degeneration in the absence of neurotrophin signaling: dendritic retraction and neuronal loss after removal of the receptor TrkB. Neuron 26: 233–45.CrossRefGoogle ScholarPubMed
Yamada, K, Mizuno, M, Nabeshima, T (2002). Role for brain-derived neurotrophic factor in learning and memory. Life Sci 70: 735–44.CrossRefGoogle ScholarPubMed
Yatham, L N, Liddle, P F, Shiah, I S, et al. (2000). Brain serotonin2 receptors in major depression: a positron emission tomography study. Arch Gen Psychiatry 57: 850–8.CrossRefGoogle ScholarPubMed
Zhou, F C, Lesch, K P, Murphy, D L (2002). Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res 942: 109–19.CrossRefGoogle ScholarPubMed

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