期刊
MOLECULAR PSYCHIATRY
卷 18, 期 4, 页码 451-460出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2013.4
关键词
Alzheimer's disease; adult hippocampal neurogenesis; GSK-3; post-synaptic density; environmental enrichment; retrovirus; PSD95
资金
- Spanish Ministry of Health [SAF 2006-02424, BFU-2008-03980, BFU-2010-21507]
- Comunidad de Madrid [SAL/0202/2006]
- Fundacion M. Botin
- Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII)
- Fundacion R Areces
Adult hippocampal neurogenesis (AHN) is crucial for the maintenance of hippocampal function. Several neurodegenerative diseases such as Alzheimer's disease (AD) are accompanied by memory deficits that could be related to alterations in AHN. Here, we took advantage of a conditional mouse model to study the involvement of glycogen synthase kinase-3 beta (GSK-3 beta) overexpression (OE) in AHN. By injecting GFP- and PSD95-GFP-expressing retroviruses, we have determined that hippocampal GSK-3 beta-OE causes dramatic alterations in both dendritic tree morphology and post-synaptic densities in newborn neurons. Alterations in previously damaged neurons were reverted by switching off the transgenic system and also by using a physiological approach (environmental enrichment) to increase hippocampal plasticity. Furthermore, comparative morphometric analysis of granule neurons from patients with AD and from GSK-3 beta overexpressing mice revealed shared morphological alterations. Taken together, these data indicate that GSK-3 beta is crucial for hippocampal function, thereby supporting this kinase as a relevant target for the treatment of AD. Molecular Psychiatry (2013) 18, 451-460; doi:10.1038/mp.2013.4; published online 12 February 2013
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