Lack of JWA Enhances Neurogenesis and Long-Term Potentiation in Hippocampal Dentate Gyrus Leading to Spatial Cognitive Potentiation
| Autor: | Ling Chen, Juan Hong, Jin Xu, Wei-Jun Qu, Jianwei Zhou, Zi-Hong Lu, Sha Sha |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Genotype Cell Survival Neurogenesis Long-Term Potentiation Neuroscience (miscellaneous) Morris water navigation task Hippocampus Hippocampal formation 03 medical and health sciences Cellular and Molecular Neuroscience Cognition 0302 clinical medicine Cell Movement Neurites LTP induction Animals Phosphorylation Protein Kinase Inhibitors Heat-Shock Proteins PI3K/AKT/mTOR pathway Mice Knockout Chemistry TOR Serine-Threonine Kinases Dentate gyrus Membrane Transport Proteins Long-term potentiation Cell biology 030104 developmental biology Animals Newborn nervous system Neurology Focal Adhesion Protein-Tyrosine Kinases Dentate Gyrus Synapses Carrier Proteins Proto-Oncogene Proteins c-akt Zidovudine Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Molecular Neurobiology. 53:355-368 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | JWA (Arl6ip5), a homologous gene of glutamate-transporter-associated protein 3-18 (GTRAP3-18) and addicsin, is highly expressed in hippocampus. We generated systemic and neuronal JWA knockout (JWA-KO and JWA-nKO) mice to investigate the influence of JWA deficiency on spatial cognitive performance, process of neurogenesis, and induction of long-term potentiation (LTP) in hippocampal dentate gyrus (DG). In comparison with wild-type (WT) mice and JWA (loxP/loxP) (control of JWA-nKO) mice, 8-week-old JWA-KO mice and JWA-nKO mice showed spatial cognitive potentiation as assessed by Morris water maze test. In hippocampal DG of JWA-nKO mice, either survival and migration or neurite growth of newborn neurons were significantly enhanced without the changes in proliferation and differentiation of stem cells. In addition, the increase of LTP amplitude and the decline of LTP threshold were observed in DG, but not in CA1 region, of JWA-nKO mice compared to control mice. The levels of hippocampal FAK, Akt, and mTOR phosphorylation in JWA-nKO mice were higher than those in control mice. The PI3K or FAK inhibitor could abolish the enhanced neurogenesis and LTP induction in JWA-nKO mice, which was accompanied by disappearance of the spatial cognitive potentiation. The treatment of JWA-nKO mice with 3'-azido-3'-deoxythymidine (AZT), a telomerase inhibitor, suppressed not only the enhanced neurogenesis but also the enhanced LTP induction in DG, but it did not affect the LTP induction in CA1 region. The results suggest that the JWA deficiency through cascading FAK-PI3K-Akt-mTOR pathway increases the newborn neurons and enhances the LTP induction in hippocampal DG, which leads to the spatial cognitive potentiation. |
| Databáze: | OpenAIRE |
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