B0AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is Involved in Mediating the Effect of Leucine in the Brain

Maria G A Hägglund, Sahar Roshanbin, Erik Löfqvist, Sofie V. Hellsten, Victor C O Nilsson, Aniruddha Todkar, Yinan Zhu, Olga Stephansson, Jana Drgonova, George R. Uhl, Helgi B. Schiöth, Robert Fredriksson

Research output: Contribution to journalArticle

Abstract

The B0AT2 protein is a product of the SLC6A15 gene belonging to the SLC6 subfamily and has been shown to be a transporter of essential branched-chain amino acids. We aimed to further characterize the B0AT2 transporter in CNS, and to use Slc6a15 knock out (KO) mice to investigate whether B0AT2 is important for mediating the anorexigenic effect of leucine. We used the Slc6a15 KO mice to investigate the role of B0AT2 in brain in response to leucine and in particular the effect on food intake. Slc6a15 KO mice show lower reduction of food intake as well as lower neuronal activation in the ventromedial hypothalamic nucleus (VMH) in response to leucine injections compared to wild type mice. We also used RT-PCR on rat tissues, in situ hybridization and immunohistochemistry on mouse CNS tissues to document in detail the distribution of SLC6A15 on gene and protein levels. We showed that B0AT2 immunoreactivity is mainly neuronal, including localization in many GABAergic neurons and spinal cord motor neurons. B0AT2 immunoreactivity was also found in astrocytes close to ventricles, and co-localized with cytokeratin and diazepam binding inhibitor (DBI) in epithelial cells of the choroid plexus. The data suggest that B0AT2 play a role in leucine homeostasis in the brain.

Original languageEnglish (US)
Article numbere58651
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 7 2013
Externally publishedYes

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astrocytes
Leucine
Astrocytes
leucine
Neurons
Brain
neurons
Knockout Mice
brain
mice
Diazepam Binding Inhibitor
Eating
Ventromedial Hypothalamic Nucleus
transporters
Tissue
food intake
GABAergic Neurons
Branched Chain Amino Acids
Choroid Plexus
Essential Amino Acids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hägglund, M. G. A., Roshanbin, S., Löfqvist, E., Hellsten, S. V., Nilsson, V. C. O., Todkar, A., ... Fredriksson, R. (2013). B0AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is Involved in Mediating the Effect of Leucine in the Brain. PLoS One, 8(3), [e58651]. https://doi.org/10.1371/journal.pone.0058651

B0AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is Involved in Mediating the Effect of Leucine in the Brain. / Hägglund, Maria G A; Roshanbin, Sahar; Löfqvist, Erik; Hellsten, Sofie V.; Nilsson, Victor C O; Todkar, Aniruddha; Zhu, Yinan; Stephansson, Olga; Drgonova, Jana; Uhl, George R.; Schiöth, Helgi B.; Fredriksson, Robert.

In: PLoS One, Vol. 8, No. 3, e58651, 07.03.2013.

Research output: Contribution to journalArticle

Hägglund, MGA, Roshanbin, S, Löfqvist, E, Hellsten, SV, Nilsson, VCO, Todkar, A, Zhu, Y, Stephansson, O, Drgonova, J, Uhl, GR, Schiöth, HB & Fredriksson, R 2013, 'B0AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is Involved in Mediating the Effect of Leucine in the Brain', PLoS One, vol. 8, no. 3, e58651. https://doi.org/10.1371/journal.pone.0058651
Hägglund, Maria G A ; Roshanbin, Sahar ; Löfqvist, Erik ; Hellsten, Sofie V. ; Nilsson, Victor C O ; Todkar, Aniruddha ; Zhu, Yinan ; Stephansson, Olga ; Drgonova, Jana ; Uhl, George R. ; Schiöth, Helgi B. ; Fredriksson, Robert. / B0AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is Involved in Mediating the Effect of Leucine in the Brain. In: PLoS One. 2013 ; Vol. 8, No. 3.
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