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Research ArticleResearch Article: New Research, Cognition and Behavior

Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice

Dirk-Jan Saaltink, Erik W. van Zwet and Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: https://doi.org/10.1523/ENEURO.0324-19.2020
Dirk-Jan Saaltink
1Department of Cell and Chemical Biology
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Erik W. van Zwet
2Department of Biomedical Data Sciences, 2333ZA Leiden University Medical Center, Leiden, The Netherlands
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Erno Vreugdenhil
1Department of Cell and Chemical Biology
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Abstract

Doublecortin (DCX)-like (DCL) is a microtubule (MT)-associated protein (MAP) that is highly homologous to DCX and is crucially involved in embryonic neurogenesis. Here, we have investigated the in vivo role of DCL in adult hippocampal neurogenesis by generating transgenic mice producing inducible shRNA molecules that specifically target DCL but no other splice variants produced by the DCLK gene. DCL knock-down (DCL-KD) resulted in a significant increase in the number of proliferating BrdU+ cells in the subgranular zone (SGZ) 1 d after BrdU administration. However, the number of surviving newborn adult NeuN+/BrdU+ neurons are significantly decreased when inspected four weeks after BrdU administration suggesting a blockade of neuronal differentiation after DCL-KD. In line with this, we observed an increase in the number of proliferating cells, but a significant decrease in postmitotic DCX+ cells that are characterized by long dendrites spanning all dentate gyrus layers. Behavioral analysis showed that DCL-KD strongly extended the escape latency of mice on the circular hole board (CHB) but did not affect other aspects of this behavioral task. Together, our results indicate a function for DCL in adult neurogenesis and in the motivation to escape from an aversive environment. In contrast to DCX, its pivotal role in the maturation of postmitotic neuronal progenitor cells (NPCs) marks DCL as a genuine adult neurogenesis indicator in the hippocampus.

  • cognition
  • DCLK1
  • doublecortin
  • hippocampus
  • neurogenesis
  • RNA interference

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported by Top Institute Pharma Project T5-210, The Netherlands.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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eneuro: 7 (5)
eNeuro
Vol. 7, Issue 5
September/October 2020
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Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice
Dirk-Jan Saaltink, Erik W. van Zwet, Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: 10.1523/ENEURO.0324-19.2020

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Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice
Dirk-Jan Saaltink, Erik W. van Zwet, Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: 10.1523/ENEURO.0324-19.2020
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Keywords

  • cognition
  • DCLK1
  • doublecortin
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  • neurogenesis
  • RNA interference

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