QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (74) Citing Articles via Google Scholar Google Scholar Articles by Cases, O. Articles by Seif, I. Search for Related Content PubMed PubMed Citation Articles by Cases, O. Articles by Seif, I.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 1, 1998, 18(17):6914-6927

Plasma Membrane Transporters of Serotonin, Dopamine, and Norepinephrine Mediate Serotonin Accumulation in Atypical Locations in the Developing Brain of Monoamine Oxidase A Knock-Outs

Olivier Cases¹, Cecile Lebrand², Bruno Giros³, Tania Vitalis¹, Edward De Maeyer⁴, Marc G. Caron⁵, David J. Price¹, Patricia Gaspar², and Isabelle Seif⁴

¹ Department of Physiology, Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland, ² Unité 106 et ³ Unité 288, Institut National de la Santé et de la Recherche Médicale, Hôpital de la Pitié-Salpêtrière, 75651 Paris Cedex 13, France, ⁴ Centre National de la Recherche Scientifique Unité Mixte de Recherche 146, Institut Curie, Bâtiment 110, 91405 Orsay Cedex, France, and ⁵ Department of Cellular Biology and Medicine, Duke University Center, Durham, North Carolina 27710

Genetic loss or pharmacological inhibition of monoamine oxidase A (MAOA) in mice leads to a large increase in whole-brain levels of serotonin (5-HT). Excess 5-HT in mouse neonates prevents the normal barrel-like clustering of thalamic axons in the somatosensory cortex. Projection fields of other neuron populations may develop abnormally. In the present study, we have analyzed the localization of 5-HT immunolabeling in the developing brain of MAOA knock-out mice. We show numerous atypical locations of 5-HT during embryonic and postnatal development. Catecholaminergic cells of the substantia nigra, ventral tegmental area, hypothalamus, and locus ceruleus display transient 5-HT immunoreactivity. Pharmacological treatments inhibiting specific monoamine plasma membrane transporters and genetic crosses with mice lacking the dopamine plasma membrane transporter show that the accumulation of 5-HT in these catecholaminergic cells is attributable to 5-HT uptake via the dopamine or the norepinephrine plasma membrane transporter. In the telencephalon, transient 5-HT immunolabeling is observed in neurons in the CA1 and CA3 fields of the hippocampus, the central amygdala, the indusium griseum, and the deep layers of the anterior cingulate and retrosplenial cortices. In the diencephalon, primary sensory nuclei, as well as the mediodorsal, centrolateral, oval paracentral, submedial, posterior, and lateral posterior thalamic nuclei, are transiently 5-HT immunolabeled. The cortical projections of these thalamic nuclei are also labeled. In the brainstem, neurons in the lateral superior olivary nucleus and the anteroventral cochlear nucleus are transiently 5-HT immunolabeled. None of these structures appear to express the monoamine biosynthetic enzyme L-aromatic amino acid decarboxylase. The administration of monoamine plasma membrane transporter inhibitors indicates that the 5-HT immunolabeling in these structures is attributable to an uptake of 5-HT by the 5-HT plasma membrane transporter. This points to neuron populations that form highly precise projection maps that could be affected by 5-HT during specific developmental stages.

Key words: monoamine oxidase; serotonin; serotonin transporter; dopamine transporter; norepinephrine transporter; brain development

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18176914-14$05.00/0

This article has been cited by other articles:

				K. Chen, O. Cases, I. Rebrin, W. Wu, T. K. Gallaher, I. Seif, and J. C. Shih Forebrain-specific Expression of Monoamine Oxidase A Reduces Neurotransmitter Levels, Restores the Brain Structure, and Rescues Aggressive Behavior in Monoamine Oxidase A-deficient Mice J. Biol. Chem., January 5, 2007; 282(1): 115 - 123. [Abstract] [Full Text] [PDF]

				T. Esaki, M. Cook, K. Shimoji, D. L. Murphy, L. Sokoloff, and A. Holmes Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice PNAS, April 12, 2005; 102(15): 5582 - 5587. [Abstract] [Full Text] [PDF]

				E. S. Vizi, G. Zsilla, M. G. Caron, and J. P. Kiss Uptake and Release of Norepinephrine by Serotonergic Terminals in Norepinephrine Transporter Knock-Out Mice: Implications for the Action of Selective Serotonin Reuptake Inhibitors J. Neurosci., September 8, 2004; 24(36): 7888 - 7894. [Abstract] [Full Text] [PDF]

				A. Rebsam, I. Seif, and P. Gaspar Refinement of Thalamocortical Arbors and Emergence of Barrel Domains in the Primary Somatosensory Cortex: A Study of Normal and Monoamine Oxidase A Knock-Out Mice J. Neurosci., October 1, 2002; 22(19): 8541 - 8552. [Abstract] [Full Text] [PDF]

				C. Gras, E. Herzog, G. C. Bellenchi, V. Bernard, P. Ravassard, M. Pohl, B. Gasnier, B. Giros, and S. El Mestikawy A Third Vesicular Glutamate Transporter Expressed by Cholinergic and Serotoninergic Neurons J. Neurosci., July 1, 2002; 22(13): 5442 - 5451. [Abstract] [Full Text] [PDF]

				B. J. A. Janssen and J. F. M. Smits Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1545 - R1564. [Abstract] [Full Text] [PDF]

				R. P. Carson and D. Robertson Genetic Manipulation of Noradrenergic Neurons J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 410 - 417. [Abstract] [Full Text] [PDF]

				B. S. Beltz, J. L. Benton, and J. M. Sullivan Transient uptake of serotonin by newborn olfactory projection neurons PNAS, October 23, 2001; 98(22): 12730 - 12735. [Abstract] [Full Text] [PDF]

				J. J. Chen, Z. Li, H. Pan, D. L. Murphy, H. Tamir, H. Koepsell, and M. D. Gershon Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters J. Neurosci., August 15, 2001; 21(16): 6348 - 6361. [Abstract] [Full Text] [PDF]

				N. Salichon, P. Gaspar, A. L. Upton, S. Picaud, N. Hanoun, M. Hamon, E. De Maeyer, D. L. Murphy, R. Mossner, K. P. Lesch, et al. Excessive Activation of Serotonin (5-HT) 1B Receptors Disrupts the Formation of Sensory Maps in Monoamine Oxidase A and 5-HT Transporter Knock-Out Mice J. Neurosci., February 1, 2001; 21(3): 884 - 896. [Abstract] [Full Text] [PDF]

				C. Bou-Flores, A.-M. Lajard, R. Monteau, E. De Maeyer, I. Seif, J. Lanoir, and G. Hilaire Abnormal Phrenic Motoneuron Activity and Morphology in Neonatal Monoamine Oxidase A-Deficient Transgenic Mice: Possible Role of a Serotonin Excess J. Neurosci., June 15, 2000; 20(12): 4646 - 4656. [Abstract] [Full Text] [PDF]

				A. L. Upton, N. Salichon, C. Lebrand, A. Ravary, R. Blakely, I. Seif, and P. Gaspar Excess of Serotonin (5-HT) Alters the Segregation of Ispilateral and Contralateral Retinal Projections in Monoamine Oxidase A Knock-Out Mice: Possible Role of 5-HT Uptake in Retinal Ganglion Cells During Development J. Neurosci., August 15, 1999; 19(16): 7007 - 7024. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help