Skip to main content
SpringerLink
Log in

DJ-1 is Essential for Long-Term Depression at Hippocampal CA1 Synapses

  • Original Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

Mutations in DJ-1 cause inherited Parkinson’s disease (PD) in several families. The normal function of DJ-1 is unknown, but mice lacking DJ-1 exhibit a deficit in dopaminergic signaling in the striatum. Since the hippocampus contains relatively high levels of DJ-1, and PD patients are often cognitively impaired, we evaluated the effects of DJ-1 deficiency on the plasticity of hippocampal CA1 synapses. LTP was slightly impaired and LTD was abolished in DJ-1−/− mice, whereas DJ-1+/− mice exhibited no alterations in synaptic plasticity. The dopamine receptor D2/3 agonist quinpirole rescued LTD in DJ-1−/− mice, suggesting a role for impaired dopaminergic signaling in the hippocampal LTD deficit.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D., & Rosenthal, A. (2000). Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25, 239–252.

    Article  PubMed  CAS  Google Scholar 

  • Bader, V., Zhu, X., Lubbert, H., & Stichel, C. C. (2005). Expression of DJ-1 in the adult mouse CNS. Brain Research, 1041, 102–111.

    Article  PubMed  CAS  Google Scholar 

  • Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., & Heutink, P. (2003). Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science, 299, 256–259.

    Article  PubMed  CAS  Google Scholar 

  • Camicioli, R., Moore, M. M., Kinney, A., Corbridge, E., Glassberg, K., & Kaye, J. A. (2003). Parkinson’s disease is associated with hippocampal atrophy. Movement Disorders, 18, 784–790.

    Article  PubMed  Google Scholar 

  • Chandran, J. S., Lin, X., Zapata, A., Shimoji, M., Hoke, A., O’Leary Moore, S., Galloway, M. P., Laird, F. M., Bailey, K. R., Shippenberg, T., Wong, P., & Cai, H. (2007). Progressive behavioral deficits in DJ-1 deficient mice are associated with normal nigrostriatal function. Neurobiology of Disease, (In press).

  • Chen, Z., Ito, K., Fujii, S., Miura, M., Furuse, H., Sasaki, H., Kaneko, K., Kato, H., & Miyakawa, H. (1996). Roles of dopamine receptors in long-term depression: Enhancement via D1 receptors and inhibition via D2 receptors. Receptors Channels, 4, 1–8.

    PubMed  CAS  Google Scholar 

  • Chen, L., Cagniard, B., Mathews, T., Jones, S., Koh, H. C., Ding, Y., Carvey, P. M., Ling, Z., Kang, U. J., & Zhuang, X. (2005). Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. The Journal of Biological Chemistry, 280, 21418–21426.

    Article  PubMed  CAS  Google Scholar 

  • Dawson, T. M., & Dawson, V. L. (2003). Molecular pathways of neurodegeneration in Parkinson’s disease. Science, 302, 819–822.

    Article  PubMed  CAS  Google Scholar 

  • Frey, U., Matthies, H., Reymann, K. G., & Matthies, H. (1991). The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro. Neuroscience Letters, 129, 111–114.

    Article  PubMed  CAS  Google Scholar 

  • Galter, D., Westerlund, M., Belin, A. C., & Olson, L. (2007). DJ-1 and UCH-L1 gene activity patterns in the brains of controls, Parkinson and schizophrenia patients and in rodents. Physiological and Behavioral Science, 92, 46–53.

    Article  CAS  Google Scholar 

  • Goldberg, M. S., Pisani, A., Haburcak, M., Vortherms, T. A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., Bernardi, G., Roth, B. L., Pothos, E. N., Calabresi, P., & Shen, J. (2005). Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron, 45, 489–496.

    Article  PubMed  CAS  Google Scholar 

  • Hague, S., Rogaeva, E., Hernandez, D., Gulick, C, Singleton, A., Hanson, M., Johnson, J., Weiser, R., Gallardo, M., Ravina, B., Gwinn-Hardy, K., Crawley, A., St George-Hyslop, P. H., Lang, A. E., Heutink, P., Bonifati, V., Hardy, J., & Singleton, A. (2003). Early-onset Parkinson’s disease caused by a compound heterozygous DJ-1 mutation. Annals of Neurology, 54, 271–274.

    Article  PubMed  CAS  Google Scholar 

  • Hardy, J., Cai, H., Cookson, M. R., Gwinn-Hardy, K., & Singleton, A. (2006). Genetics of Parkinson’s disease and parkinsonism. Annals of Neurology, 60, 389–398.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Y. Y., & Kandel, E. R. (1995). D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 92, 2446–2450.

    Article  PubMed  CAS  Google Scholar 

  • Kerr, D. S., & Abraham, W. C. (1995). Cooperative interactions among afferents govern the induction of homosynaptic long-term depression in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 92, 11637–11641.

    Article  PubMed  CAS  Google Scholar 

  • Kitada, T., Asakawa, S., & Hattori, N. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 392, 605–608.

    Article  PubMed  CAS  Google Scholar 

  • Kitada, T., Pisani, A., Porter, D. R., Yamaguchi, H., Tscherter, A., Martella, G., Bonsi, P., Zhang, C., Pothos, E. N., & Shen, J. (2007). Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 104, 11441–11446.

    Article  PubMed  CAS  Google Scholar 

  • Kotaria, N., Hinz, U., Zechel, S., & von Bohlen Und Halbach, O. (2005). Localization of DJ-1 protein in the murine brain. Cell and Tissue Research, 322, 503–507.

    Article  PubMed  CAS  Google Scholar 

  • Lemon, N., & Manahan-Vaughan, D. (2006). Dopamine D1/D5 receptors gate the acquisition of novel information through hippocampal long-term potentiation and long-term depression. The Journal of Neuroscience, 26, 7723–7729.

    Article  PubMed  CAS  Google Scholar 

  • Li, S., Cullen, W. K., Anwyl, R., & Rowan, M. J. (2003). Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nature Neuroscience, 6, 526–531.

    PubMed  CAS  Google Scholar 

  • Norris, C. M., Korol, D. L., & Foster, T. C. (1996). Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. The Journal of Neuroscience, 16, 5382–5392.

    PubMed  CAS  Google Scholar 

  • Otmakhova, N. A., & Lisman, J. E. (1998). D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism. The Journal of Neuroscience, 18, 1270–1279.

    PubMed  CAS  Google Scholar 

  • Savitt, J. M., Dawson, V. L., & Dawson, T. M. (2006). Diagnosis and treatment of Parkinson disease: Molecules to medicine. The Journal of Clinical Investigation, 16, 1744–1754.

    Article  Google Scholar 

  • Shang, H., Lang, D., Jean-Marc, B., & Kaelin-Lang, A. (2004). Localization of DJ-1 mRNA in the mouse brain. Neuroscience Letters, 367, 273–277.

    Article  PubMed  CAS  Google Scholar 

  • Swant, J., & Wagner, J. J. (2006). Dopamine transporter blockade increases LTP in the CA1 region of the rat hippocampus via activation of the D3 dopamine receptor. Learning & Memory, 13, 161–167.

    Article  CAS  Google Scholar 

  • Turle-Lorenzo, N., Maurin, B., Puma, C., Chezaubernard, C., Morain, P., Baunez, C., Nieoullon, A., & Amalric, M. (2006). The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: Relevance for Parkinson’s disease. JPET, 319, 914–923.

    Article  CAS  Google Scholar 

  • Valente, E. M., Abou-Sleiman, P. M., & Caputo, V. (2004). Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science, 304, 1158–1160.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., Chan, S. L., Miele, L., Yao, P. J., Mackes, J., Ingram, D. K., Mattson, M. P., & Furukawa, K. (2004). Involvement of Notch signaling in hippocampal synaptic plasticity. Proceedings of the National Academy of Sciences of the United States of America, 101, 9458–9462.

    Article  PubMed  CAS  Google Scholar 

  • Wilkerson, A., & Levin, E. D. (1999). Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in rats. Neuroscience, 89, 743–749.

    Article  PubMed  CAS  Google Scholar 

  • Williams-Gray, C. H., Foltynie, T., & Brayne, C. E. (2007). Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain, 130, 1787–1798.

    Article  PubMed  CAS  Google Scholar 

  • Yavich, L., Tanila, H., Vepsalainen, S., & Jakala, P. (2004). Role of alpha-synuclein in presynaptic dopamine recruitment. The Journal of Neuroscience, 24, 11165–11170.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We thank the Comparative Medicine Section of NIA for technical support. The authors declare that they have no competing financial interest.

Author information

Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA

    Yue Wang & Mark P. Mattson

  2. Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Yue Wang

  3. Laboratory of Neurogenetics, National Institute on Aging Intramural Research Program, Baltimore, MD, USA

    Jayanth S. Chandran & Huaibin Cai

  4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Mark P. Mattson

Authors
  1. Yue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jayanth S. Chandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huaibin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark P. Mattson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yue Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Y., Chandran, J.S., Cai, H. et al. DJ-1 is Essential for Long-Term Depression at Hippocampal CA1 Synapses. Neuromol Med 10, 40–45 (2008). https://doi.org/10.1007/s12017-008-8023-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-008-8023-4

Keywords

Search

Navigation