Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex |
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Authors: | Long-Jun Wu Susan S Kim Xiangyao Li Fuxing Zhang Min Zhuo |
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Institution: | 1. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA 2. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA 3. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA 5. Bioimaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, 500-712, Republic of Korea 4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
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Abstract: | Background Neural stem cells (NSCs) are present in the adult mammalian brain and sustain life-long adult neurogenesis in the dentate gyrus of the hippocampus. In culture, fibroblast growth factor-2 (FGF-2) is sufficient to maintain the self-renewal of adult NSCs derived from the adult rat hippocampus. The underlying signalling mechanism is not fully understood. Results In the established adult rat NSC culture, FGF-2 promotes self-renewal by increasing proliferation and inhibiting spontaneous differentiation of adult NSCs, accompanied with activation of MAPK and PLC pathways. Using a molecular genetic approach, we demonstrate that activation of FGF receptor 1 (FGFR1), largely through two key cytoplasmic amino acid residues that are linked to MAPK and PLC activation, suffices to promote adult NSC self-renewal. The canonical MAPK, Erk1/2 activation, is both required and sufficient for the NSC expansion and anti-differentiation effects of FGF-2. In contrast, PLC activation is integral to the maintenance of adult NSC characteristics, including the full capacity for neuronal and oligodendroglial differentiation. Conclusion These studies reveal two amino acid residues in FGFR1 with linked downstream intracellular signal transduction pathways that are essential for maintaining adult NSC self-renewal. The findings provide novel insights into the molecular mechanism regulating adult NSC self-renewal, and pose implications for using these cells in potential therapeutic applications. |
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