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Open Access Highly Accessed Research article

Newly generated cells are increased in hippocampus of adult mice lacking a serine protease inhibitor

Maddalena M Lino1, Catherine Vaillant1, Slobodanka Orolicki1, Melanie Sticker3, Mirna Kvajo2 and Denis Monard1*

Author Affiliations

1 Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland

2 Psychiatric Institute, Department of Psychiatry, Columbia University, New York, NY 10032, USA

3 Novartis Pharma AG, Klybeckstrasse 141, CH-4057 Basel, Switzerland

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BMC Neuroscience 2010, 11:70  doi:10.1186/1471-2202-11-70

Published: 8 June 2010

Abstract

Background

Neurogenesis in the hippocampal dentate gyrus and the subventricular zone occurs throughout the life of mammals and newly generated neurons can integrate functionally into established neuronal circuits. Neurogenesis levels in the dentate gyrus are modulated by changes in the environment (enrichment, exercise), hippocampal-dependent tasks, NMDA receptor (NMDAR) activity, sonic hedgehog (SHH) and/or other factors.

Results

previously, we showed that Protease Nexin-1 (PN-1), a potent serine protease inhibitor, regulates the NMDAR availability and activity as well as SHH signaling. Compared with wild-type (WT), we detected a significant increase in BrdU-labeled cells in the dentate gyrus of mice lacking PN-1 (PN-1 -/-) both in controls and after running exercise. Patched homologue 1 (Ptc1) and Gli1 mRNA levels were higher and Gli3 down-regulated in mutant mice under standard conditions and to a lesser extent after running exercise. However, the number of surviving BrdU-positive cells did not differ between WT and PN-1 -/- animals. NMDAR availability was altered in the hippocampus of mutant animals after exercise.

Conclusion

All together our results indicate that PN-1 controls progenitors proliferation through an effect on the SHH pathway and suggest an influence of the serpin on the survival of newly generated neurons through modulation of NMDAR availability.