Your browser doesn't support javascript.
loading
Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95/Discs Large/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity.
Ni, Huan-Yu; Song, Yi-Xuan; Lin, Yu-Hui; Cao, Bo; Wang, Dong-Liang; Zhang, Yu; Dong, Jian; Liang, Hai-Ying; Xu, Ke; Li, Ting-You; Chang, Lei; Wu, Hai-Yin; Luo, Chun-Xia; Zhu, Dong-Ya.
Affiliation
  • Ni HY; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Song YX; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Lin YH; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Cao B; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Wang DL; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Zhang Y; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Dong J; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Liang HY; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Xu K; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Li TY; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Chang L; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Wu HY; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Luo CX; From the Institution of Stem Cells and Neuroregeneration (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
  • Zhu DY; Department of Pharmacology, School of Pharmacy (H.-Y.N., Y.-X.S., Y.-H.L., B.C., D.-L.W., Y.Z., J.D., H.-Y.L., K.X., T.-Y.L., L.C., H.-Y.W., C.-X.L., D.-Y.Z.), Nanjing Medical University, China.
Stroke ; 50(3): 728-737, 2019 03.
Article in En | MEDLINE | ID: mdl-30727847
ABSTRACT
Background and Purpose- Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95/discs large/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery. Methods- Photothrombotic stroke and transient middle cerebral artery occlusion were induced in mice. Adeno-associated virus (AAV)-cytomegalovirus (CMV)-CAPON-125C-GFP (green fluorescent protein)-3Flag and the other 2 drugs (Tat-CAPON-12C and ZLc-002) were microinjected into the peri-infarct cortex immediately and 4 to 10 days after photothrombotic stroke, respectively. ZLc-002 was also systemically injected 4 to 10 days after transient middle cerebral artery occlusion. Grid-walking task and cylinder task were conducted to assess motor function. Western blotting, immunohistochemistry, Golgi staining, and electrophysiology recordings were performed to uncover the mechanisms. Results- Stroke increased nNOS-CAPON association in the peri-infarct cortex in the delayed period. Inhibiting the ischemia-induced nNOS-CAPON association substantially decreased the number of foot faults in the grid-walking task and forelimb asymmetry in the cylinder task, suggesting the promotion of functional recovery from stroke. Moreover, dissociating nNOS-CAPON significantly facilitated dendritic remodeling and synaptic transmission, indicated by increased dendritic spine density, dendritic branching, and length and miniature excitatory postsynaptic current frequency but did not affect stroke-elicited neuronal loss, infarct size, or cerebral edema, suggesting that nNOS-CAPON interaction may function via regulating structural neuroplasticity, rather than neuroprotection. Furthermore, ZLc-002 reversed the transient middle cerebral artery occlusion-induced impairment of motor function. Conclusions- Our results reveal that nNOS-CAPON coupling can serve as a novel pharmacological target for functional restoration after stroke.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stroke / Adaptor Proteins, Signal Transducing / Nitric Oxide Synthase Type I / Neuronal Plasticity Limits: Animals Language: En Journal: Stroke Year: 2019 Document type: Article Affiliation country: China
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stroke / Adaptor Proteins, Signal Transducing / Nitric Oxide Synthase Type I / Neuronal Plasticity Limits: Animals Language: En Journal: Stroke Year: 2019 Document type: Article Affiliation country: China