Interaction of nNOS with PSD-95 Negatively Controls Regenerative Repair after Stroke

Luo, Chunxia; Lin, Yu Hui; Qian, Xiaodan; Tang, Ying; Zhou, Hai-Hui; Jin, Xing; Ni, Huan‐Yu; Zhang, Fengyun; Cheng, Qi; Li, Fēi; Zhang, Yu; Wu, Hai‐Yin; Chang, Lei; Zhu, Dong‐Ya

doi:10.1523/jneurosci.1305-14.2014

Cited by 73 publications

(93 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4,18 Before experiments, we did correlation analysis between cerebral blood flow decline and neuroscore after MCAO to control transient MCAO efficacy. There was a positive correlation between neuroscore and the percentage of cerebral blood flow decline after stroke (n=14; R=−0.931; P<0.001; Figure I in the online-only data Supplement).…”

Section: Surgical Preparationmentioning

confidence: 99%

“…Modified Neurological Severity Score test, 19 Morris water maze task, Barnes circular maze, grid-walking task, and cylinder task 18 were performed as previously reported (more details are available in Methods in the online-only data Supplement).…”

Section: Behavioral Assessmentmentioning

confidence: 99%

“…Immunofluorescence was performed as we previously reported 18 (more details are available in Methods in the online-only data Supplement).…”

Section: Immunofluorescencementioning

confidence: 99%

See 2 more Smart Citations

Delayed Administration of Tat-HA-NR2B9c Promotes Recovery After Stroke in Rats

Zhou

Tang

Zhang

et al. 2015

Stroke

View full text Add to dashboard Cite

Background and Purpose— Previous studies reported that Tat-NR2B9c, a peptide disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction, reduced ischemic damage in the acute phase after stroke. However, its effect in the subacute phase is unknown. The aim of this study is to determine whether disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction in the subacute phase promotes recovery after stroke. Methods— Studies were performed on Sprague-Dawley rats or nNOS −/− mice, and experimental ischemic stroke was induced by middle cerebral artery occlusion. Animals were treated with drugs starting at day 4 after ischemia. Sensorimotor functions and spatial learning and memory ability were assessed after drug treatment. Then, rats were euthanized for morphological observation and biochemical tests. Results— Disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction with Tat-HA-NR2B9c significantly ameliorated the ischemia-induced impairments of spatial memory and sensorimotor functions in rats during subacute stage but did not improve stroke outcome in nNOS −/− mice. Consistent with the functional recovery, Tat-HA-NR2B9c substantially increased neurogenesis in the dentate gyrus and dendritic spine density of mature neurons in the motor cortex of rats, meanwhile, reversed the ischemia-induced formation of S -nitrosylation-cyclin-dependent kinase 5 and increased cyclin-dependent kinase 5 activity in ipsilateral hippocampus. However, directly blocking N -methyl- d -aspartate receptors with MK-801 or Ro 25-6981 did not show the beneficial effects above. Conclusions— Dissociating N -methyl- d -aspartate receptor–postsynaptic density protein-95 coupling by Tat-HA-NR2B9c in the subacute phase after stroke promotes functional recovery, probably because of that it increases neurogenesis and dendritic spine density of mature neurons via regulating cyclin-dependent kinase 5 in the ischemic brain.

show abstract

Section: Surgical Preparationmentioning

confidence: 99%

Section: Behavioral Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Delayed Administration of Tat-HA-NR2B9c Promotes Recovery After Stroke in Rats

Zhou

Tang

Zhang

et al. 2015

Stroke

View full text Add to dashboard Cite

show abstract

“…The details of immunofluorescence for brain sections and cultured cells have been described (Luo et al., 2014). Briefly, brain slices were fixed in 4% paraformaldehyde (30 μm) and cultured cells were blocked with blocking solution (10% serum of donkey, 0.2% Triton X‐100).…”

Section: Methodsmentioning

confidence: 99%

nNOS–CAPON interaction mediates amyloid‐β‐induced neurotoxicity, especially in the early stages

et al. 2018

View full text Add to dashboard Cite

SummaryIn neurons, increased protein–protein interactions between neuronal nitric oxide synthase (nNOS) and its carboxy‐terminal PDZ ligand (CAPON) contribute to excitotoxicity and abnormal dendritic spine development, both of which are involved in the development of Alzheimer's disease. In models of Alzheimer's disease, increased nNOS–CAPON interaction was detected after treatment with amyloid‐β in vitro, and a similar change was found in the hippocampus of APP/PS1 mice (a transgenic mouse model of Alzheimer's disease), compared with age‐matched background mice in vivo. After blocking the nNOS–CAPON interaction, memory was rescued in 4‐month‐old APP/PS1 mice, and dendritic impairments were ameliorated both in vivo and in vitro. Furthermore, we demonstrated that S‐nitrosylation of Dexras1 and inhibition of the ERK–CREB–BDNF pathway might be downstream of the nNOS–CAPON interaction.

show abstract

“…NO derived from GluN2B/PSd-95/nNOS signaling not only mediates NMdAR-dependent excitotoxicity but also inhibits regenerative repair via the regulation of histone deacetylase 2 during the recovery stage. 6 Blocking NO production derived from nNOS by interfering with the formation of the GluN2B/PSd-95/nNOS complex may be a promising strategy. Tat-NR2B9c, which comprises the cell-membrane transduction domain of the HIV-1 Tat protein and the 9 C-terminal residues of GluN2B, is the first reported peptide that perturbs NMdAR-PSd-95 protein interaction.…”

Section: Glun2b/psd-95/nnos Complexmentioning

confidence: 99%