Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity

Haruki Odaka, Tadahiro Numakawa, Naoki Adachi, Yoshiko Ooshima, Shingo Nakajima, Yusuke Katanuma, Takafumi Inoue, Hiroshi Kunugi

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Several lines of evidence demonstrate that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent antioxidants may therefore be effective in the treatment of such diseases. Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been studied using several cell types including mesencephalic neurons, and is recognized as a potent radical scavenger. Here, we examined whether cabergoline exerts neuroprotective effects against oxidative stress through a receptor-mediated mechanism in cultured cortical neurons. We found that neuronal death induced by H2O2 exposure was inhibited by pretreatment with cabergoline, while this protective effect was eliminated in the presence of a dopamine D2 receptor inhibitor, spiperone. Activation of ERK1/2 by H2O2 was suppressed by cabergoline, and an ERK signaling pathway inhibitor, U0126, similarly protected cortical neurons from cell death. This suggested the ERK signaling pathway has a critical role in cabergoline-mediated neuroprotection. Furthermore, increased extracellular levels of glutamate induced by H2O2, which might contribute to ERK activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L-type Ca2+ channel demonstrated a survival effect against H2O2. Interestingly, we found that cabergoline increased expression levels of glutamate transporters such as EAAC1. Taken together, these results suggest that cabergoline has a protective effect on cortical neurons via a receptor-mediated mechanism including repression of ERK1/2 activation and extracellular glutamate accumulation induced by H2O2.

    Original languageEnglish
    Article numbere99271
    JournalPLoS One
    Volume9
    Issue number6
    DOIs
    Publication statusPublished - 2014 Jun 10

    Fingerprint

    Oxidative stress
    Dopamine D2 Receptors
    Dopamine Agonists
    Cell death
    dopamine
    agonists
    cell death
    Oxidative Stress
    Cell Death
    oxidative stress
    neurons
    receptors
    glutamates
    Neurons
    protective effect
    MAP Kinase Signaling System
    Chemical activation
    neuroprotective effect
    Parkinson disease
    free radical scavengers

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Odaka, H., Numakawa, T., Adachi, N., Ooshima, Y., Nakajima, S., Katanuma, Y., ... Kunugi, H. (2014). Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. PLoS One, 9(6), [e99271]. https://doi.org/10.1371/journal.pone.0099271

    Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. / Odaka, Haruki; Numakawa, Tadahiro; Adachi, Naoki; Ooshima, Yoshiko; Nakajima, Shingo; Katanuma, Yusuke; Inoue, Takafumi; Kunugi, Hiroshi.

    In: PLoS One, Vol. 9, No. 6, e99271, 10.06.2014.

    Research output: Contribution to journalArticle

    Odaka, Haruki ; Numakawa, Tadahiro ; Adachi, Naoki ; Ooshima, Yoshiko ; Nakajima, Shingo ; Katanuma, Yusuke ; Inoue, Takafumi ; Kunugi, Hiroshi. / Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. In: PLoS One. 2014 ; Vol. 9, No. 6.
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