Doublecortin-like knockdown in the adult mouse brain: implications for neurogenesis, neuroplasticity and behaviour

Saaltink, D.J. (2014)

Doctoral Thesis

The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely hypothalamic tanycytes, suprachiasmatic nucleus and Islands of Calleja. A state of the art conditional shRNA expressing mouse model was used to target DCL mRNA. The analysis of these DCL knockdown animals using qPCR and Western blot revealed strong reduction of DCL protein expression. Subsequent stereological analysis using BrdU and several stem cell and neuronal markers revealed increased progenitor proliferation, but impaired neurogenesis in the hippocampus. This impaired neurogenesis was associated, however, with an apparent normal spatial and contextual fear memory formation in circular hole board and in a contextual fear conditioning paradigm. Therefore, DCL-regulated adult neurogenesis seems not crucial for hippocampus-dependent learning. However, more subtle functions like pattern separation and context distinction might be regulated by DCL. DCL knockdown also increased D2 activity within the hypothalamus. Altogether, the DCL-KD mouse seems a good working model to study adult neurogenesis and the role of DCL in this process.

• Learning and memory
• Brain
• Doublecortin-like
• Hypothalamus
• Transgenic mouse
• Behaviour
• siRNA
• Hippocampus
• Neurogenesis

• All authors: Saaltink, D.J.
• Supervisor: Kloet, E.R. de
• Co-supervisor: Vreugdenhil, E.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine (LUMC), Leiden University
• Date: 2014-06-05
• ISBN (print): 9789088918704
• Sponsorship: TI Pharma