THESIS
2014
xi, 59 pages : illustrations (some color) ; 30 cm
Abstract
Adult neurogenesis, a process of generating new functional neurons throughout
adulthood, is crucial for the organization and functioning of the brain. In particular,
adult neurogenesis in the hippocampus plays important roles in various brain
functions, such as spatial learning and possibly affective processes. Impairment of
adult neurogenesis has been observed in a variety of models related to affective or
cognitive disorders including major depression and Alzheimer’s disease, respectively.
To ensure the proper progression of adult neurogenesis, amplification and
differentiation of adult neural progenitors is precisely co-ordinated by multiple
signaling pathways including the Wnt signaling pathway. Originally identified as a
negative regulator of conical Wnt signaling pathway,...[
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Adult neurogenesis, a process of generating new functional neurons throughout
adulthood, is crucial for the organization and functioning of the brain. In particular,
adult neurogenesis in the hippocampus plays important roles in various brain
functions, such as spatial learning and possibly affective processes. Impairment of
adult neurogenesis has been observed in a variety of models related to affective or
cognitive disorders including major depression and Alzheimer’s disease, respectively.
To ensure the proper progression of adult neurogenesis, amplification and
differentiation of adult neural progenitors is precisely co-ordinated by multiple
signaling pathways including the Wnt signaling pathway. Originally identified as a
negative regulator of conical Wnt signaling pathway, Axin regulates tumorigenesis,
axis development and embryonic cortical neurogenesis through interaction with
different components of Wnt signaling pathway. Nonetheless, it remains unclear
whether and how Axin modulates adult neurogenesis. Here, we report that Axin is
highly expressed in adult mouse brains, particularly at the dentate gyrus of
hippocampus, the region where adult neurogenesis occurs. Increasing the Axin protein
level in adult mouse brains promoted the proliferation of adult neural progenitors and
enhanced the survival of newly-born cells in dentate gyrus region. Besides, we found
that retrovirus-mediated knockdown of Axin impaired dendrite growth of newly born
neurons in vivo during hippocampal neurogenesis.Furthermore, we demonstrated that
increased protein level of Axin ameliorated the depression symptoms of mice in a
battery of behavioral tests. These findings suggested that Axin is critical for the
regulation of adult hippocampal neurogenesis and related depressive behavior. In
future studies, we aim to examine the underlying mechanism of Axin in adult
neurogenesis
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