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Lack of JWA Enhances Neurogenesis and Long-Term Potentiation in Hippocampal Dentate Gyrus Leading to Spatial Cognitive Potentiation

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Abstract

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.

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References

  1. Huang S et al (2006) JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun 341:440–450. doi:10.1016/j.bbrc.2005.12.197

    Article  CAS  PubMed  Google Scholar 

  2. Butchbach ME, Lai L, Lin CL (2002) Molecular cloning, gene structure, expression profile and functional characterization of the mouse glutamate transporter (EAAT3) interacting protein GTRAP3-18. Gene 292:81–90. doi:10.1016/S0378-1119(02)00669-8

    Article  CAS  PubMed  Google Scholar 

  3. Ikemoto MJ et al (2002) Identification of addicsin/GTRAP3-18 as a chronic morphine-augmented gene in amygdala. Neuroreport 13:2079–2084. doi:10.1097/00001756-200211150-00018

    Article  CAS  PubMed  Google Scholar 

  4. Inoue K, Akiduki S, Ikemoto MJ (2005) Expression profile of addicsin/GTRAP3-18 mRNA in mouse brain. Neurosci Lett 386:184–188. doi:10.1016/j.neulet.2005.06.013

    Article  CAS  PubMed  Google Scholar 

  5. Akiduki S, Ochiishi T, Ikemoto MJ (2007) Neural localization of addicsin in mouse brain. Neurosci Lett 426:149–154. doi:10.1016/j.neulet.2007.08.056

    Article  CAS  PubMed  Google Scholar 

  6. Aoyama K et al (2012) Increased neuronal glutathione and neuroprotection in GTRAP3-18-deficient mice. Neurobiol Dis 45:973–982. doi:10.1016/j.nbd.2011.12.016

    Article  CAS  PubMed  Google Scholar 

  7. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034. doi:10.1038/4151030a

    Article  PubMed  Google Scholar 

  8. Christie BR, Cameron HA (2006) Neurogenesis in the adult hippocampus. Hippocampus 16:199–207. doi:10.1002/hipo.20151

    Article  CAS  PubMed  Google Scholar 

  9. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:372–376. doi:10.1038/35066584

    Article  CAS  PubMed  Google Scholar 

  10. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385–14390. doi:10.1073/pnas.2334169100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bruel-Jungerman E, Laroche S, Rampon C (2005) New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur J Neurosci 21:513–521. doi:10.1111/j.1460-9568.2005.03875.x

    Article  PubMed  Google Scholar 

  12. Shen L, Xu W, Li A, Ye J, Zhou J (2011) JWA enhances As(2)O(3)-induced tubulin polymerization and apoptosis via p38 in HeLa and MCF-7 cells. Apoptosis 16:1177–1193. doi:10.1007/s10495-011-0637-6

    Article  CAS  PubMed  Google Scholar 

  13. Chen H et al (2007) JWA as a functional molecule to regulate cancer cells migration via MAPK cascades and F-actin cytoskeleton. Cell Signal 19:1315–1327. doi:10.1016/j.cellsig.2007.01.007

    Article  CAS  PubMed  Google Scholar 

  14. Bai J et al (2010) JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling. Oncogene 29:1227–1237. doi:10.1038/onc.2009.408

    Article  CAS  PubMed  Google Scholar 

  15. Rozengurt E (2007) Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol 213:589–602. doi:10.1002/jcp.21246

    Article  CAS  PubMed  Google Scholar 

  16. Schweneker M, Bachmann AS, Moelling K (2005) JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Lett 579:1751–1758. doi:10.1016/j.febslet.2005.02.037

    Article  CAS  PubMed  Google Scholar 

  17. Ruggiero AM et al (2008) The endoplasmic reticulum exit of glutamate transporter is regulated by the inducible mammalian Yip6b/GTRAP3-18 protein. J Biol Chem 283:6175–6183. doi:10.1074/jbc.M701008200

    Article  CAS  PubMed  Google Scholar 

  18. Gong Z et al (2012) JWA deficiency suppresses dimethylbenz[a]anthracene-phorbol ester induced skin papillomas via inactivation of MAPK pathway in mice. PLoS One 7:e34154. doi:10.1371/journal.pone.0034154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sha S et al (2013) Sigma-1 receptor knockout impairs neurogenesis in dentate gyrus of adult hippocampus via down-regulation of NMDA receptors. CNS Neurosci Ther 19:705–713. doi:10.1111/cns.12129

    Article  CAS  PubMed  Google Scholar 

  20. Chatterjee S et al (2013) A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice. J Neurosci 33:10698–10712. doi:10.1523/JNEUROSCI. 5772-12.2013

    Article  CAS  PubMed  Google Scholar 

  21. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184–187. doi:10.1038/nature02553

    Article  CAS  PubMed  Google Scholar 

  22. Golubovskaya VM et al (2008) A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth. J Med Chem 51:7405–7416. doi:10.1021/jm800483v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou QG et al (2011) Hippocampal telomerase is involved in the modulation of depressive behaviors. J Neurosci 31:12258–12269. doi:10.1523/JNEUROSCI. 0805-11.2011

    Article  CAS  PubMed  Google Scholar 

  24. Butchbach ME, Guo H, Lin CL (2003) Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3-mediated glutamate uptake and increases GTRAP3-18 expression. J Neurochem 84:891–894. doi:10.1046/j.1471-4159.2003.01588.x

    Article  CAS  PubMed  Google Scholar 

  25. Tashiro A, Makino H, Gage FH (2007) Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J Neurosci 27:3252–3259

    Article  CAS  PubMed  Google Scholar 

  26. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94:991–1026. doi:10.1152/physrev.00004.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Olariu A, Cleaver KM, Shore LE, Brewer MD, Cameron HA (2005) A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus. Hippocampus 15:750–762. doi:10.1002/hipo.20097

    Article  PubMed  Google Scholar 

  28. Aoyama K, Nakaki T (2012) Inhibition of GTRAP3-18 may increase neuroprotective glutathione (GSH) synthesis. Int J Mol Sci 13:12017–12035. doi:10.3390/ijms130912017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mao WG, Liu ZL, Chen R, Li AP, Zhou JW (2006) JWA is required for the antiproliferative and pro-apoptotic effects of all-trans retinoic acid in Hela cells. Clin Exp Pharmacol Physiol 33:816–824. doi:10.1111/j.1440-1681.2006. 04446.x

    Article  CAS  PubMed  Google Scholar 

  30. Zhou J, Ye J, Zhao X, Li A (2008) JWA is required for arsenic trioxide induced apoptosis in HeLa and MCF-7 cells via reactive oxygen species and mitochondria linked signal pathway. Toxicol Appl Pharmacol 230:33–40. doi:10.1016/ j.taap.2008.01.041

    Article  CAS  PubMed  Google Scholar 

  31. Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3–11. doi:10.1523/JNEUROSCI. 3648-05.2006

    Article  CAS  PubMed  Google Scholar 

  32. Dayer AG, Ford AA, Cleaver KM, Yassaee M, Cameron HA (2003) Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 460:563–572. doi:10.1002/cne.10675

    Article  PubMed  Google Scholar 

  33. Tashiro A, Sandler VM, Toni N, Zhao C, Gage FH (2006) NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442:929–933. doi:10.1038/nature05028

    Article  CAS  PubMed  Google Scholar 

  34. Yang R, Zhou R, Chen L, Cai W, Tomimoto H, Sokabe M (2011) Pregnenolone sulfate enhances survival of adult-generated hippocampal granule cells via sustained presynaptic potentiation. Neuropharmacology 60:529–541. doi:10.1016/j.neuropharm.2010.11.017

    Article  CAS  PubMed  Google Scholar 

  35. Maier S et al (2009) GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation. J Cell Mol Med 13:114–124. doi:10.1111/j.1582-4934.2008.00303.x

    Article  CAS  PubMed  Google Scholar 

  36. Feron F et al (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65:141–148. doi:10.1016/j.brainresbull.2004.12.007

    Article  CAS  PubMed  Google Scholar 

  37. Chen TJ, Wang DC, Chen SS (2009) Amyloid-beta interrupts the PI3K-Akt-mTOR signaling pathway that could be involved in brain-derived neurotrophic factor-induced Arc expression in rat cortical neurons. J Neurosci Res 87:2297–2307. doi:10.1002/jnr.22057

    Article  CAS  PubMed  Google Scholar 

  38. Liu R et al (2008) Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology. J Cell Mol Med 12:241–257. doi:10.1111/j.1582-4934.2008.00249.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li L, Xu B, Zhu Y, Chen L, Sokabe M (2010) DHEA prevents Abeta25-35 impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling. Neuropharmacology 59:323–333. doi:10.1016/j.neuropharm.2010.02.009

    Article  CAS  PubMed  Google Scholar 

  40. Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11:339–350. doi:10.1038/nrn2822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang Z, Yang R, Zhou R, Li L, Sokabe M, Chen L (2010) Progesterone promotes the survival of newborn neurons in the dentate gyrus of adult male mice. Hippocampus 20:402–412. doi:10.1002/hipo.20642

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants for National 973 Basic Research Program of China (grant no. 2014CB943303), National Nature Science Foundation of China (grant nos. 81071027, 31171440 and 81361120247) to Chen L, National Nature Science Foundation of China (grant nos. 30930080 and 91229125) to Zhou JW.

Disclosure statement

We declare that there is no competing financial interest that could be construed as influencing the results or interpretation of the reported study.

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Authors and Affiliations

  1. Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210029, China

    Sha Sha & Ling Chen

  2. Department of Physiology, Nanjing Medical University, Hanzhong Road 140, Nanjing, Jiangsu, 210029, China

    Sha Sha, Zi-Hong Lu, Juan Hong, Wei-Jun Qu & Ling Chen

  3. Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Hanzhong Road 140, Nanjing, Jiangsu, 210029, China

    Jin Xu & Jian-Wei Zhou

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  1. Sha Sha
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Correspondence to Jian-Wei Zhou or Ling Chen.

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Sha, S., Xu, J., Lu, ZH. et al. Lack of JWA Enhances Neurogenesis and Long-Term Potentiation in Hippocampal Dentate Gyrus Leading to Spatial Cognitive Potentiation. Mol Neurobiol 53, 355–368 (2016). https://doi.org/10.1007/s12035-014-9010-4

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