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


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: 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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