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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 and Sreedharan, Smitha and Nordenankar, Karin and Alsio, Johan and Lindberg, Frida A. and Hutchinson, Ashley and Eriksson, Anders and Roshanbin, Sahar and Ciuculete, Diana M. and Klockars, Anica and Todkar, Aniruddha and Hagglund, Maria G. and Hellsten, Sofie and Hindlycke, Viktoria and Vastermark, Ake and Shevchenko, Ganna and Olivo, Gaia and Cheng, Ken and Kullander, Klas and Moazzami, Ali and Bergquist, Jonas and Olszewski, Pawel K. and Schioth, Helgi B. (2019). The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain. PLoS Genetics. 15 , 1-30
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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.

Authors/Creators:Fredriksson, Robert and Sreedharan, Smitha and Nordenankar, Karin and Alsio, Johan and Lindberg, Frida A. and Hutchinson, Ashley and Eriksson, Anders and Roshanbin, Sahar and Ciuculete, Diana M. and Klockars, Anica and Todkar, Aniruddha and Hagglund, Maria G. and Hellsten, Sofie and Hindlycke, Viktoria and Vastermark, Ake and Shevchenko, Ganna and Olivo, Gaia and Cheng, Ken and Kullander, Klas and Moazzami, Ali and Bergquist, Jonas and Olszewski, Pawel K. and Schioth, Helgi B.
Title:The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain
Year of publishing :2019
Volume:15
Page range:1-30
Number of Pages:30
Publisher:PLoS
ISSN:1553-7390
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Neurosciences
Keywords:polyamine transporters, Slc18b1, nerve cells, memory, learning, Long Term Potentiation
URN:NBN:urn:nbn:se:slu:epsilon-p-104555
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-104555
Additional ID:
Type of IDID
DOI10.1371/journal.pgen.1008455
Web of Science (WoS)000512336600007
ID Code:16714
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:30 Mar 2020 08:28
Metadata Last Modified:30 Mar 2020 08:28

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