ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice.

Abstract

BACKGROUND:

ATP-binding cassette (ABC) transporters are essential regulators of organismic homeostasis, and are particularly important in protecting the body from potentially harmful exogenous substances. Recently, an increasing number of in vitro observations have indicated a functional role of ABC transporters in the differentiation and maintenance of stem cells. Therefore, we sought to determine brain-related phenotypic changes in animals lacking the expression of distinct ABC transporters (ABCB1, ABCG2 or ABCC1).

METHODOLOGY AND PRINCIPAL FINDINGS:

Analyzing adult neurogenesis in ABC transporter-deficient animals in vivo and neuronal stem/progenitor cells in vitro resulted in complex findings. In vivo, the differentiation of neuronal progenitors was hindered in ABC transporter-deficient mice (ABCB1(0/0)) as evidenced by lowered numbers of doublecortin(+) (-36%) and calretinin(+) (-37%) cells. In vitro, we confirmed that this finding is not connected to the functional loss of single neural stem/progenitor cells (NSPCs). Furthermore, assessment of activity, exploratory behavior, and anxiety levels revealed behavioral alterations in ABCB1(0/0) and ABCC1(0/0) mice, whereas ABCG2(0/0) mice were mostly unaffected.

CONCLUSION AND SIGNIFICANCE:

Our data show that single ABC transporter-deficiency does not necessarily impair neuronal progenitor homeostasis on the single NSPC level, as suggested by previous studies. However, loss of distinct ABC transporters impacts global brain homeostasis with far ranging consequences, leading to impaired neurogenic functions in vivo and even to distinct behavioral phenotypes. In addition to the known role of ABC transporters in proteopathies such as Parkinson's disease and Alzheimer's disease, our data highlight the importance of understanding the general function of ABC transporters for the brain's homeostasis and the regeneration potential.

• Authors: Toni Schumacher, Markus Krohn, Jacqueline Hofrichter, Cathleen Lange, Jan Stenzel, Johannes Steffen, Tina Dunkelmann, Kristin Paarmann, Christina Fröhlich, Annekathrin Uecker, Anne-Sophie Plath, Alexandra Sommer, Thomas Brüning, Hans-Jochen Heinze, Jens Pahnke
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e35613 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22545122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Abcg2 protein, mouse
• Multidrug Resistance-Associated Proteins
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Anxiety (genetics, metabolism)
• Behavior, Animal
• Brain (cytology, metabolism)
• Cell Proliferation
• Cells, Cultured
• Female
• Gene Deletion
• Male
• Mice
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Neurogenesis
• Neurons (cytology, metabolism)
• Stem Cells (cytology, metabolism)