Skip to main content
Research article - Peer-reviewed, 2019

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

Fredriksson, Robert; Sreedharan, Smitha; Nordenankar, Karin; Alsio, Johan; Lindberg, Frida A.; Hutchinson, Ashley; Eriksson, Anders; Roshanbin, Sahar; Ciuculete, Diana M.; Klockars, Anica; Todkar, Aniruddha; Hagglund, Maria G.; Hellsten, Sofie, V; Hindlycke, Viktoria; Vastermark, Ake; Shevchenko, Ganna; Olivo, Gaia; Cheng, K.; Kullander, Klas; Moazzami, Ali;
Show more authors

Abstract

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.

Keywords

polyamine transporters; Slc18b1; nerve cells; memory; learning; Long Term Potentiation

Published in

PLoS Genetics
2019, volume: 15, number: 12, article number: e1008455
Publisher: PUBLIC LIBRARY SCIENCE

Authors' information

Fredriksson, Robert
Uppsala University
Sreedharan, Smitha
Uppsala University
Nordenankar, Karin
Uppsala University
Alsio, Johan
Uppsala University
Lindberg, Frida A.
Uppsala University
Hutchinson, Ashley
Uppsala University
Eriksson, Anders
Uppsala University
Roshanbin, Sahar
Uppsala University
Ciuculete, Diana M.
Uppsala University
Klockars, Anica
University of Waikato
Todkar, Aniruddha
Uppsala University
Hagglund, Maria G.
Uppsala University
Hellsten, Sofie
Uppsala University
Hindlycke, Viktoria
Uppsala University
Vastermark, Ake
Uppsala University
Shevchenko, Ganna
Uppsala University
Olivo, Gaia
Uppsala University
Cheng, Ken
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Kullander, Klas
Uppsala University
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Show more authors

UKÄ Subject classification

Neurosciences

Publication Identifiers

DOI: https://doi.org/10.1371/journal.pgen.1008455

URI (permanent link to this page)

https://res.slu.se/id/publ/104555