Alpha-chimaerin limited axonal sprouting and functional recovery post-stroke
作者单位：The Joint Research Center of Biomedicine Wenzhou University and Wenzhou Medical University The Institute of Life Sciences Wenzhou University The Institute of Neuroscience and Chemistry Wenzhou University Department of Neurology David Geffen School of Medicine University of California Los Angeles The Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University
会议名称：《中国神经科学学会第十二届全国学术会议》
会议日期：2017年
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
摘 要：Axonal sprouting in peri-infarct cortex is associated with functional recovery after stroke. With high-throughput gene expression analysis of single sprouting neurons, upregulation of α-chimaerin, a Rho GTPase-activating protein, has been identified during the initiation of axonal sprouting in somatosensory cortex after stroke of aged animals. To define the functional roles of α-chimaerin in axonal sprouting, gain-and loss-of-function strategies were employed in the present studies. We first examined the effect of α-chimaerin in axonal outgrowth of the primary neurons. Quantitative analysis indicated that α-chimaerin si RNA duplex significantly enhanced axonal outgrowth, while α-chimaerin-GFP（lentiviral constructs carrying a whole sequence of the α-chimaerin gene linked to the GFP） suppressed axonal outgrowth of the neurons in vitro compared to the controls, respectively. We further tested the role of α-chimaerin on axonal sprouting in vivo in peri-infarct cortex using a mouse photothrombotic cortical stroke model. The duplex of α-chimaerin/control si RNA or the lentiviral α-chimaerin/control-GFP was respectively injected into a region of motor cortex that mediates recovery after stroke（Li et al., Nat Neurosci 2015） at 1 week following focal cortical stroke. Animals were sacrificed 3 weeks after the si RNA or lentiviral transfection and the tissue processed in tangential cortical sections to visualize the mouse somatosensory cortical map. There was no significant difference in axonal sprouting between α-chimaerin si RNA and scrambled non-stroke mice. However, stroke animals administrated with α-chimaerin si RNA duplex shown a significant increase of axonal connections in the peri-infarct cortex in comparing with the stroke scrambled-treated mice. In contrast, axonal sprouting in α-chimaerinGFP treated group was significantly inhibited when compared to the lentiviral-GFP control group, reducing new patterns of connections in premotor and motor cortex and in first and