Anatomical and behavioral impact of a lentiviral tool tapping onto hippocampal serotonin reuptake in rats.

5-HT7 receptor Porsolt's forced swim test dentate gyrus elevated plus maze (EPM) in vivo gene silencing magnetic resonance spectroscopy (1H-MRS) novelty seeking test serotonin transporter (SERT) social interaction test (SIT)

Journal

Synapse (New York, N.Y.)
ISSN: 1098-2396
Titre abrégé: Synapse
Pays: United States
ID NLM: 8806914

Informations de publication

Date de publication:
04 2020
Historique:
received: 16 07 2019
revised: 23 09 2019
accepted: 30 09 2019
pubmed: 7 10 2019
medline: 11 8 2021
entrez: 7 10 2019
Statut: ppublish

Résumé

We aimed at the further characterization of rats in which SERT gene silencing was achieved by hippocampal injection of a lentiviral vector, carrying three si-RNA to block SERT mRNA at 66% of normal levels. Improved self-control and reduced restlessness were already demonstrated in these rats. Present further studies consisted of male adult rats, bilaterally inoculated within the hippocampus; control rats received lentivirus particles inactivated with heat. Both groups were maintained in isolation for 5 months, starting from inoculation. Neurochemical changes were studied by proton magnetic resonance spectroscopy (1H-MRS): we found increased hippocampal viability and bioenergetic potential; however, rats showed a behaviorally depressive pattern, also characterized by enhanced affiliation. Based on the extent of such effects, the whole lenti-SERT group was divided into two subgroups, termed intermediate- and extreme- phenotype profiles. While all rats had a widespread modification within dorsal/ventral striatum, amygdala, and hypothalamus, only the former subgroup showed an involvement of Raphé medialis, while, for the latter subgroup, an increase of SERT within hippocampus was unexpectedly caused. Within the less-affected "intermediate" rats, hippocampal 5-HT7 receptors were down-modulated, and also similarly within substantia nigra, septum, and neocortex. This picture demonstrates that additional rather than fewer neurobiological changes accompany a lower phenotypic expression. Overall, tapping hippocampal SERT affected the balance between habits versus strategies of coping by promoting morphogenetic processes indicative of a serotonergic fiber plasticity. Supplementary studies about serotonergic dynamics and neurogenesis within fronto-striatal circuits are needed.

Identifiants

pubmed: 31587367
doi: 10.1002/syn.22138
doi:

Substances chimiques

RNA-Binding Proteins 0
Receptors, Serotonin 0
Sert1 protein, rat 0
serotonin 7 receptor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e22138

Informations de copyright

© 2019 Wiley Periodicals, Inc.

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Auteurs

Francesca Zoratto (F)

Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

Clelia Buccheri (C)

Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

Romina Mura (R)

Faculty of Psychology, "Uninettuno" International Telematic University, Rome, Italy.

Luisa Altabella (L)

Core Facilities, Istituto Superiore di Sanità, Rome, Italy.

Marion Vanneste (M)

Normandie Univ. UNICAEN, Inserm, Comete, GIP Cyceron, Caen, France.

Marie Villotte (M)

Normandie Univ. UNICAEN, Inserm, Comete, GIP Cyceron, Caen, France.

Giovanni Laviola (G)

Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

Francois Dauphin (F)

Normandie Univ. UNICAEN, Inserm, Comete, GIP Cyceron, Caen, France.

Eleni Paizanis (E)

Normandie Univ. UNICAEN, Inserm, Comete, GIP Cyceron, Caen, France.

Walter Adriani (W)

Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.
Faculty of Psychology, "Uninettuno" International Telematic University, Rome, Italy.

Rossella Canese (R)

Core Facilities, Istituto Superiore di Sanità, Rome, Italy.

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