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

BMC Neuroscience

Research Article

Diane Lagace¹  Amelia Eisch²  Flavia Antonucci³  Harold Cremer⁴  Matteo Caleo⁵  Yuri Bozzi⁶  Tariq Ahmed⁷  Detlef Balschun⁷  Rudi D'Hooge⁷  Veerle Reumers⁸  Veerle Baekelandt⁸  Astrid DeVriese⁹  Jonathan Cremer⁹  Vanessa Coremans⁹  Tom Janssens⁹  Michaël Moons⁹  Edward M Conway^1,10 

[1] Department of Cellular and Molecular Medicine & Neuroscience Program, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, Canada;Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, 75390-9070, Dallas, Texas, USA;Dept of Pharmacology, University of Milan, via Vanvitelli 32, Milan, Italy;Developmental Biology Institute of Marseille, NMDA CNRS, INSERM, Univ. de Mediterranee, Campus de Luminy, 13288, Marseille, France;Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via G. Moruzzi 1, 56100, Pisa, Italy;Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via G. Moruzzi 1, 56100, Pisa, Italy;Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, via delle Regole 101, 38060, Trento, Italy;KU Leuven Laboratory of Biological Psychology, Tiensestraat 102, B3000, Leuven, Belgium;KU Leuven, Laboratory for Neurobiology and Gene Therapy, Kapucijnenvoer 33, B3000, Leuven, Belgium;KU Leuven, VIB Vesalius Research Center (VRC), Herestraat 49, Gasthuisberg O&N1, B3000, Leuven, Belgium;KU Leuven, VIB Vesalius Research Center (VRC), Herestraat 49, Gasthuisberg O&N1, B3000, Leuven, Belgium;Center for Blood Research, Faculty of Medicine, University of British Columbia, 2350 Health Sciences Mall, V6T 1Z3, Vancouver, Canada;

关键词: Conditioned Stimulus;    Olfactory Bulb;    Dentate Gyrus;    Kainic Acid;    Survivin Expression;   

DOI  :  10.1186/1471-2202-11-2

 received in 2009-07-24, accepted in 2010-01-05,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSurvivin 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.ResultsTo 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. SurvivinCamcrebrains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning.ConclusionsThe findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

【 授权许可】

Unknown   
© Coremans et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.