Characterize the functional roles of Axin in adult neurogenesis

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, 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

Date of Award	2014
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology