Yi Zhang1, Yi Qin1, Michael Chopp1,2, Chao Li1, Amy Kemper3, Xianshuang Liu1, Xinli Wang1, Li Zhang1, Zheng Gang Zhang1. 1. Department of Neurology (Y.Z., Y.Q., M.C., C.L., X.L., X.W., L.Z., Z.G.Z.), Henry Ford Hospital, Detroit, MI. 2. Department of Physics, Oakland University, Rochester, MI (M.C.). 3. Department of Pathology (A.K.), Henry Ford Hospital, Detroit, MI.
Abstract
BACKGROUND AND PURPOSE: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. METHODS: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. RESULTS: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo-altered miRNAs and proteins in somata but not in distal axons. CONCLUSIONS: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.
BACKGROUND AND PURPOSE: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. METHODS: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. RESULTS: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo-altered miRNAs and proteins in somata but not in distal axons. CONCLUSIONS: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.
Authors: Hua Teng; Zheng Gang Zhang; Lei Wang; Rui Lan Zhang; Li Zhang; Dan Morris; Sara R Gregg; Zhenhua Wu; Angela Jiang; Mei Lu; Berislav V Zlokovic; Michael Chopp Journal: J Cereb Blood Flow Metab Date: 2007-10-31 Impact factor: 6.200
Authors: Li Zhang; Chao Li; Rui Huang; Hua Teng; Yi Zhang; Min Zhou; Xiangshuang Liu; Baoyan Fan; Hao Luo; Annie He; Anna Zhao; Mei Lu; Michael Chopp; Zheng Gang Zhang Journal: Front Aging Neurosci Date: 2022-07-14 Impact factor: 5.702
Authors: Yi Zhang; Chao Li; Yi Qin; Pasquale Cepparulo; Michael Millman; Michael Chopp; Amy Kemper; Alexandra Szalad; Xuerong Lu; Lei Wang; Zheng Gang Zhang Journal: J Extracell Vesicles Date: 2021-03-04