Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β.

Gayle H. Doherty, Dayne Beccano-Kelly, Shi-Du Yan, Frank Gunn-Moore, Jenni Harvey (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    70 Citations (Scopus)

    Abstract

    Accumulation of amyloid-ß (Aß) is a key event mediating the cognitive deficits in Alzheimer's disease (AD) as Aß promotes synaptic dysfunction and triggers neuronal death. Recent evidence has linked the hormone leptin to AD as leptin levels are markedly attenuated in AD patients. Leptin is also a potential cognitive enhancer as it facilitates the cellular events underlying hippocampal learning and memory. Here we show that leptin prevents the detrimental effects of Aß1–42 on hippocampal long-term potentiation. Moreover leptin inhibits Aß1–42-driven facilitation of long-term depression and internalization of the 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA) receptor subunit, GluR1, via activation of PI3-kinase. Leptin also protects cortical neurons from Aß1–42-induced cell death by a signal transducer and activator of transcription-3 (STAT-3)-dependent mechanism. Furthermore, leptin inhibits Aß1–42-mediated upregulation of endophilin I and phosphorylated tau in vitro, whereas cortical levels of endophilin I and phosphorylated tau are enhanced in leptin-insensitive Zucker fa/fa rats. Thus leptin benefits the functional characteristics and viability of neurons that degenerate in AD. These novel findings establish that the leptin system is an important therapeutic target in neurodegenerative conditions.
    Original languageEnglish
    Pages (from-to)226-37
    JournalNeurobiology of Aging
    Volume34
    Issue number1
    DOIs
    Publication statusPublished - Jan 2013

    Fingerprint

    Leptin
    Amyloid
    Cell Death
    Alzheimer Disease
    Nootropic Agents
    Neurons
    STAT3 Transcription Factor
    Long-Term Potentiation
    Phosphatidylinositol 3-Kinases
    Up-Regulation
    Learning
    Hormones
    Depression

    Keywords

    • Leptin
    • SYNAPTIC PLASTICITY
    • AMPA receptor trafficking
    • Amyloid beta
    • Endophilin

    Cite this

    Doherty, Gayle H. ; Beccano-Kelly, Dayne ; Yan, Shi-Du ; Gunn-Moore, Frank ; Harvey, Jenni. / Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 1. pp. 226-37.
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    Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β. / Doherty, Gayle H.; Beccano-Kelly, Dayne; Yan, Shi-Du; Gunn-Moore, Frank; Harvey, Jenni (Lead / Corresponding author).

    In: Neurobiology of Aging, Vol. 34, No. 1, 01.2013, p. 226-37.

    Research output: Contribution to journalArticle

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