All-trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer's mouse model

Risa Takamura, Naoto Watamura, Miyu Nikkuni, Toshio Ohshima

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/PS1M146V/tauP301L (3×Tg) mice. We observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 3×Tg mouse brains at 12 months of age. Previously, our research had shown an anti-inflammatory effect of all-trans retinoic acid (ATRA) in the 3×Tg mouse brain. We found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model.

    Original languageEnglish
    JournalJournal of Neuroscience Research
    DOIs
    Publication statusAccepted/In press - 2016

    Fingerprint

    Neural Stem Cells
    Tretinoin
    Neurogenesis
    Hippocampus
    Alzheimer Disease
    Inflammation
    Amyloid Plaques
    Brain
    Microglia
    Neurodegenerative Diseases
    Anti-Inflammatory Agents
    Research

    Keywords

    • Adult neurogenesis
    • Alzheimer's disease
    • Model mouse
    • Neuroinflammation
    • Retinoic acid

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

    Cite this

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    title = "All-trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer's mouse model",
    abstract = "Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/PS1M146V/tauP301L (3×Tg) mice. We observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 3×Tg mouse brains at 12 months of age. Previously, our research had shown an anti-inflammatory effect of all-trans retinoic acid (ATRA) in the 3×Tg mouse brain. We found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model.",
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    author = "Risa Takamura and Naoto Watamura and Miyu Nikkuni and Toshio Ohshima",
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    AU - Watamura, Naoto

    AU - Nikkuni, Miyu

    AU - Ohshima, Toshio

    PY - 2016

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    AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/PS1M146V/tauP301L (3×Tg) mice. We observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 3×Tg mouse brains at 12 months of age. Previously, our research had shown an anti-inflammatory effect of all-trans retinoic acid (ATRA) in the 3×Tg mouse brain. We found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model.

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    KW - Model mouse

    KW - Neuroinflammation

    KW - Retinoic acid

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