The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.


Journal

PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074

Informations de publication

Date de publication:
12 2019
Historique:
received: 11 12 2018
accepted: 03 10 2019
revised: 23 12 2019
pubmed: 5 12 2019
medline: 4 3 2020
entrez: 5 12 2019
Statut: epublish

Résumé

SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.

Identifiants

pubmed: 31800589
doi: 10.1371/journal.pgen.1008455
pii: PGENETICS-D-18-02327
pmc: PMC6927659
doi:

Substances chimiques

Cation Transport Proteins 0
Polyamines 0
vesicular polyamine transporter, mouse 0
Glutamic Acid 3KX376GY7L
gamma-Aminobutyric Acid 56-12-2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008455

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Robert Fredriksson (R)

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Smitha Sreedharan (S)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Karin Nordenankar (K)

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Johan Alsiö (J)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Frida A Lindberg (FA)

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Ashley Hutchinson (A)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Anders Eriksson (A)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Sahar Roshanbin (S)

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Diana M Ciuculete (DM)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Anica Klockars (A)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Faculty of Science and Engineering, University of Waikato, Hamilton, New Zealand.

Aniruddha Todkar (A)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Maria G Hägglund (MG)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Sofie V Hellsten (SV)

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Viktoria Hindlycke (V)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Åke Västermark (Å)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Ganna Shevchenko (G)

Department of Chemistry, Uppsala University, Uppsala, Sweden.

Gaia Olivo (G)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Cheng K (C)

Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Klas Kullander (K)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.

Ali Moazzami (A)

Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Jonas Bergquist (J)

Department of Chemistry, Uppsala University, Uppsala, Sweden.

Pawel K Olszewski (PK)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Faculty of Science and Engineering, University of Waikato, Hamilton, New Zealand.

Helgi B Schiöth (HB)

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.

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