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Regulation of astrocyte pathology by fluoxetine prevents the deterioration of Alzheimer phenotypes in an APP/PS 1 mouse model
Author(s) -
Qiao Jinping,
Wang Junhui,
Wang Hongxing,
Zhang Yanbo,
Zhu Shenghua,
Adilijiang Abulimiti,
Guo Huining,
Zhang Ruiguo,
Guo Wei,
Luo Gang,
Qiu Yiqing,
Xu Haiyun,
Kong Jiming,
Huang Qingjun,
Li XinMin
Publication year - 2016
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22926
Subject(s) - astrocyte , fluoxetine , neuroscience , phenotype , biology , alzheimer's disease , hippocampal formation , pathology , medicine , central nervous system , disease , receptor , gene , serotonin , genetics
Studies have implicated astrocytic dysfunction in Alzheimer's disease (AD). However, the role of astrocytes in the pathophysiology and treatment of the disease is poorly characterized. Here, we identified astrocytes as independent key factors involved in several Alzheimer‐like phenotypes in an APP/PS1 mouse model, including amyloid pathology, altered neuronal and synaptic properties, and impaired cognition. In vitro astrocytes from APP/PS1 mice induced synaptotoxicity as well as reduced dendritic complexity and axonal branching of hippocampal neurons. These astrocytes produced high levels of soluble β‐amyloid (Aβ) which could be significantly inhibited by fluoxetine (FLX) via activating serotonin 5‐HT 2 receptors. FLX could also protect hippocampal neurons against astrocyte‐induced neuronal damage in vitro . In the same APP/PS1 mice, FLX inhibited activation of astrocytes, lowered Aβ products, ameliorated neurotoxicity, and improved behavioral performance. These findings may provide a basis for the clinical application of FLX in patients, and may also lay the groundwork for exploration of other novel astrocyte‐based therapies of AD. GLIA 2016;64:240–254