A selective CB2R agonist (JWH133) restores neuronal circuit after Germinal Matrix Hemorrhage in the preterm via CX3CR1+ microglia.

作者: Jun Tang , Hongping Miao , Bing Jiang , Qianwei Chen , Liang Tan

DOI: 10.1016/J.NEUROPHARM.2017.01.027

关键词:

摘要: Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective. However, transformation way by which neuron-microglia dialogue remain unclear. We raise hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates CX3CR1+ microglia secreting factors restores damaged neuronal circuit. Here, we report novel function of JWH133 in transforming CX3CR1 positive secrete brain-derived factor (BDNF), triggers neuron proliferation restoration. Using collagen VII-induced GMH model rat pups postnatal day 7 (P7), found drug showed robust activity precursors. Moreover, FA value DTI internal zone revealed effects on neural CX3CR1, critical modulating molecule expressed microglia, was upregulated treatment with corresponding shRNA (NM_133534.1) used to silence expression CX3CR1. 3 days JWH133, detected reduced biomarkers for progenitor cells (NPCs) pre-injected lateral ventricular tissue shRNA, but not injected control shRNA. Overall, this study provides evidence promoted (CX3CR1+ microglia), beyond merely alleviating microglial inflammation. restored impaired circuit, represent therapeutic strategy following clinic.

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