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      Homeostatic Regulation of Serotonergic Function by the Serotonin Transporter As Revealed by Nonviral Gene Transfer

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          Abstract

          With the aim of exploring the relationship between the serotonin transporter (5-HTT or SERT) and the activity level of serotonin (5-HT) neurotransmission, in vivo expression of this protein was specifically altered using a nonviral DNA transfer method. Plasmids containing the entire coding sequence or a partial antisense sequence of the 5-HTT gene were complexed with the cationic polymer polyethylenimine and injected into the dorsal raphe nucleus of adult male rats. Significant increase or decrease in both [ 3H]citalopram binding and [ 3H]5-HT synaptosomal uptake were observed in various brain areas up to 2 weeks after a single administration of the sense plasmid or 7 d after injection of the short antisense plasmid, respectively. Such changes in 5-HTT expression were associated with functional alterations in 5-HT neurotransmission, as shown by the increased capacity of 5-HT 1A receptor stimulation to enhance [ 35S]GTP-γ-S binding onto the dorsal raphe nucleus in sections from rats injected with the sense plasmid. Conversely, both a decrease in 5-HT 1A-mediated [ 35S]GTP-γ-S binding and a reduced potency of the 5-HT 1A receptor agonist ipsapirone to inhibit neuronal firing were observed in the dorsal raphe nucleus of antisense plasmid-injected rats. Furthermore, changes in brain 5-HT and/or 5-HIAA levels, and sleep wakefulness circadian rhythm in the latter animals demonstrated that altered expression of 5-HTT by recombinant plasmids has important functional consequences on central 5-HT neurotransmission in adult rats.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          1 July 2000
          : 20
          : 13
          : 5065-5075
          Affiliations
          [ 1 ]Institut National de la Santé et de la Recherche Médicale U288, Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 75634 Paris Cedex 13, France, and
          [ 2 ]Laboratoire de Physiologie Générale et Comparée, Unité de Recherche Associée 90, Centre National de la Recherche Scientifique, Museum National d'Histoire Naturelle, 75231 Paris Cedex 5, France
          Article
          PMC6772284 PMC6772284 6772284 4271
          10.1523/JNEUROSCI.20-13-05065.2000
          6772284
          10864964
          Copyright © 2000 Society for Neuroscience
          Categories
          ARTICLE
          Behavioral/Systems
          Custom metadata
          5.00

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