Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin. - Archive ouverte HAL Access content directly
Journal Articles BMC Neuroscience Year : 2010

Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin.

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Vanessa Coremans
  • Function : Author
  • PersonId : 898400
Tariq Ahmed
  • Function : Author
  • PersonId : 898401
Detlef Balschun
  • Function : Author
  • PersonId : 898402
Rudi d'Hooge
  • Function : Author
  • PersonId : 898403
Astrid Devriese
  • Function : Author
  • PersonId : 898404
Jonathan Cremer
  • Function : Author
  • PersonId : 898405
Flavia Antonucci
  • Function : Author
  • PersonId : 898406
Michaël Moons
  • Function : Author
  • PersonId : 898407
Harold Cremer
  • Function : Author
  • PersonId : 898410
Diane Lagace
  • Function : Author
  • PersonId : 898412
Tom Janssens
  • Function : Author
  • PersonId : 898413
Matteo Caleo
  • Function : Author
  • PersonId : 898415

Abstract

Background: Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results: To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions: The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.
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inserm-00582386 , version 1 (01-04-2011)

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Vanessa Coremans, Tariq Ahmed, Detlef Balschun, Rudi d'Hooge, Astrid Devriese, et al.. Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin.. BMC Neuroscience, 2010, 11 (1), pp.2. ⟨10.1186/1471-2202-11-2⟩. ⟨inserm-00582386⟩

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