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

English version

Autoři: Robert Fredriksson ^aff001; Smitha Sreedharan ^aff002; Karin Nordenankar ^aff001; Johan Alsiö ^aff002; Frida A. Lindberg ^aff001; Ashley Hutchinson ^aff002; Anders Eriksson ^aff002; Sahar Roshanbin ^aff001; Diana M. Ciuculete ^aff002; Anica Klockars ^aff002; Aniruddha Todkar ^aff002; Maria G. Hägglund ^aff002; Sofie V. Hellsten ^aff001; Viktoria Hindlycke ^aff002; Åke Västermark ^aff002; Ganna Shevchenko ^aff003; Gaia Olivo ^aff002; Cheng K ^aff004; Klas Kullander ^aff002; Ali Moazzami ^aff004; Jonas Bergquist ^aff003; Pawel K. Olszewski ^aff002; Helgi B. Schiöth ^aff002
Působiště autorů: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden ^aff001; Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden ^aff002; Department of Chemistry, Uppsala University, Uppsala, Sweden ^aff003; Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden ^aff004; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia ^aff005
Vyšlo v časopise: The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008455
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008455

Souhrn

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.

Klíčová slova:

Animal behavior – Cognitive impairment – Gamma-aminobutyric acid – Glutamate – Memory – Mice – Nose – Diazepam

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