The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how...The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.展开更多
Neuroin fil ammation contributes to neuronal death in cerebral ischemia.Urolithin A(UA),a gut microbial metabolite of ellagic acid,has emerged as a potential antiinflammatory agent.However,its roles and precise mechan...Neuroin fil ammation contributes to neuronal death in cerebral ischemia.Urolithin A(UA),a gut microbial metabolite of ellagic acid,has emerged as a potential antiinflammatory agent.However,its roles and precise mechanisms in stroke remain unknown.Riphenyltetrazolium chloride(TTC)staining was employed to assess cerebral infarct volume.The Morris water maze was used to detect cognitive function.A terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)assay was performed to detect neuronal apoptosis.展开更多
基金supported by the National Natural Science Foundation of China,No.31800892(to JLZ)the Natural Science Foundation of Guangdong Province of China,No.2018A030310254(to YY)a grant from Guangzhou Medical University Start-up Project of China,No.B195002002048(to JLZ)。
文摘The formation of nerve bundles,which is partially regulated by neural cell adhesion molecule 1(NCAM1),is important for neural network organization during peripheral nerve regeneration.However,little is known about how the extracellular matrix(ECM)microenvironment affects this process.Here,we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrixgel,Matrigel,laminin 521,collagen I,and collagen IV,and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment.We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon.A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation.Collagen VI interacted with NCAM1 by directly binding to the FNIII domain,thereby increasing the stability of NCAM1 at the axolemma.Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/m L Matrigel and 20μg/m L collagen VI.These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation.This study was approved by the Animal Ethics Committee of Guangzhou Medical University(approval No.GY2019048)on April 30,2019.
文摘Neuroin fil ammation contributes to neuronal death in cerebral ischemia.Urolithin A(UA),a gut microbial metabolite of ellagic acid,has emerged as a potential antiinflammatory agent.However,its roles and precise mechanisms in stroke remain unknown.Riphenyltetrazolium chloride(TTC)staining was employed to assess cerebral infarct volume.The Morris water maze was used to detect cognitive function.A terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)assay was performed to detect neuronal apoptosis.
