Zhao Y.,Shanghai University |
Liu X.-Z.,Shanghai University |
Tian W.-W.,Shanghai University |
Guan Y.-F.,Shanghai University |
And 3 more authors.
CNS Neuroscience and Therapeutics | Year: 2014
Aim: Visfatin, a novel adipokine, is predominantly produced by visceral adipose tissue and exists in intracellular and extracellular compartments. The intracellular form of visfatin is proved to be nicotinamide phosphoribosyltransferase (NAMPT) and exhibits neuroprotection through maintaining intracellular NAD+ pool. However, whether extracellular form of visfatin has NAMPT activity and the effect of extracellular visfatin in cerebral ischemia are unknown. Methods and Results: Plasma concentrations of visfatin, NAD+, and ATP were increased in mice upon cerebral ischemia. Cultured glia, but not neuron, was able to secrete visfatin. Oxygen-glucose deprivation (OGD) stress increased the secretion of visfatin from glia. Extracellular recombinant mouse wild-type visfatin, but not mouse H247A-mutant enzymatic-dead visfatin, had NAMPT enzymatic function in vitro. Treatment of wild-type visfatin, but not H247A-mutant enzymatic-dead visfatin, significantly attenuated detrimental effect of OGD on the cell viability and apoptosis in both cultured mouse neuron and glia. Treatment of neutralizing antibody, abolished the protective effect of extracellular visfatin on cell viability, but failed to block the antiapoptotic effect of extracellular visfatin. At last, we observed that plasma visfatin concentrations decreased in 6-month-old but not 3-month-old SHR-SP compared with that in age-matched Wistar-Kyoto rats. Inhibition of NAMPT enzymatic function of visfatin (by FK866) accelerated the occurrence of stroke in SHR-SP. Conclusions: Extracellular visfatin has NAMPT enzymatic activity and maybe be neuroprotective just as intracellular visfatin in cerebral ischemic injury. © 2014 John Wiley & Sons Ltd.
Xu X.,CAS Institute of Biophysics |
Duan S.,CAS Institute of Biophysics |
Yi F.,Salk Institute for Biological Studies |
Ocampo A.,Salk Institute for Biological Studies |
And 5 more authors.
Cell Metabolism | Year: 2013
Due to their fundamental role in energy production, mitochondria have been traditionally known as the powerhouse of the cell. Recent discoveries have suggested crucial roles of mitochondria in the maintenance of pluripotency, differentiation, and reprogramming of induced pluripotent stem cells (iPSCs). While glycolytic energy production is observed at pluripotent states, an increase in mitochondrial oxidative phosphorylation is necessary for cell differentiation. Consequently, a transition from somatic mitochondrial oxidative metabolism to glycolysis seems to be required for successful reprogramming. Future research aiming to dissect the roles of mitochondria in the establishment and homeostasis of pluripotency, as well as combining cell reprogramming with gene editing technologies, may unearth novel insights into our understanding of mitochondrial diseases and aging. © 2013 Elsevier Inc.
Liu M.-G.,PLA Fourth Military Medical University |
Liu M.-G.,Seoul National University |
Liu M.-G.,King's College |
Chen J.,PLA Fourth Military Medical University |
And 2 more authors.
Progress in Neurobiology | Year: 2014
Affective disorders and cognitive deficits are common comorbidities of chronic pain in the clinical setting, which severely affect the quality of life of pain patients and impose a great difficulty upon clinical pain therapy. Despite large numbers of human studies examining this issue, there are surprisingly few reports investigating the comorbidities of chronic pain in animal models. This review summarizes and integrates previous reports of animal studies on pain and comorbidity, covering pain-evoked anxiety, depression, attentional deficits, cognitive impairment and locomotor dysfunction in rodents. Moreover, pain-induced alterations in synaptic plasticity are also discussed in terms of long-term potentiation and long-term depression, synaptic transmission, neuronal excitability and structural correlates in 'pain matrix'. Finally, we conclude this review by pointing out some unresolved problems and future research directions. © 2014 Elsevier Ltd.
Sun Y.,Capital Medical University |
Yang F.-C.,Tri Service General Hospital |
Lin C.-P.,National Yang Ming University |
Han Y.,Capital Medical University |
Han Y.,Beijing Institute for Brain Disorders
CNS Neuroscience and Therapeutics | Year: 2015
Neurodegeneration due to Alzheimer's disease (AD) can progress over decades before dementia becomes apparent. Indeed, patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. In most cases, MCI is preceded by subjective cognitive decline (SCD), which is applied to individuals who have self-reported memory-related complaints and has been associated with a higher risk of future cognitive decline and conversion to dementia. Based on the schema of a well-received model of biomarker dynamics in AD pathogenesis, it has been postulated that SCD symptoms may result from compensatory changes in response to β-amyloid accumulation and neurodegeneration. Although SCD is considered a prodromal stage of MCI, it is also a common manifestation in old age, independent of AD, and the predictive value of SCD for AD pathology remains controversial. Here, we provide a review focused on the contributions of cross-sectional and longitudinal analogical studies of biomarkers and neuroimaging evidence in disentangling under what conditions SCD may be attributable to AD pathology. In conclusion, there is promising evidence indicating that clinicians should be able to differentiate pre-AD SCD based on the presence of pathophysiological biomarkers in cerebrospinal fluid (CSF) and neuroimaging. However, this neuroimaging approach is still at an immature stage without an established rubric of standards. A substantial amount of work remains in terms of replicating recent findings and validating the clinical utility of identifying SCD. © 2015 John Wiley & Sons Ltd.
Du L.,CAS Institute of Chemistry |
Li J.,CAS Institute of Biophysics |
Chen C.,CAS Institute of Biophysics |
Chen C.,Beijing Institute for Brain Disorders |
Liu Y.,CAS Institute of Chemistry
Free Radical Research | Year: 2014
Antioxidants are believed to have great potential for the treatment of diseases that are induced by oxidative stress. However, their pharmaceutical application is severely limited by their poor bioavailability and low biocompatibility. To solve this problem, the antioxidants can be encapsulated or covalently linked with nanomaterials to form nanoantioxidants. In this review, we aim to summarize the use of nanocarriers for antioxidant delivery and discuss their enhancement of antioxidant activity. We also suggest future research directions toward bringing nanoantioxidants into the realm of clinical applications. © 2014 Informa UK, Ltd.
Wang L.,CAS Institute of Biophysics |
Wu J.,Salk Institute for Biological Studies |
Fang W.,Beijing Hospital of the Ministry of Health |
Liu G.-H.,CAS Institute of Biophysics |
And 3 more authors.
Cell Research | Year: 2015
The CRISPR/Cas system has proven to be a powerful gene editing tool both in vitro and in vivo. A recent flurry of studies of in vivo gene editing using the CRISPR/Cas system bring bright prospects in creating animal models and targeted gene therapy of human genetic diseases. © 2015 IBCB, SIBS, CAS All rights reserved.
Peng S.,CAS Institute of Biophysics |
Peng S.,Beijing Institute for Brain Disorders |
Peng S.,University of Chinese Academy of Sciences |
Zhao S.,CAS Institute of Biophysics |
And 8 more authors.
Journal of Neuroscience | Year: 2015
All neurodegenerative diseases are associated with oxidative stress-induced neuronal death. Forkhead box O3a (FOXO3a) is a key transcription factor involved in neuronal apoptosis. However,howFOXO3aforms complexes and functions in oxidative stress processing remains largely unknown. In the present study, we show that histone deacetylase 2 (HDAC2) forms a physical complex with FOXO3a, which plays an important role in FOXO3a-dependent gene transcription and oxidative stress-induced mouse cerebellar granule neuron (CGN) apoptosis. Interestingly, we also found that HDAC2 became selectively enriched in the promoter region of the p21 gene, but not those of other target genes, and inhibited FOXO3a-mediated p21 transcription. Furthermore, we found that oxidative stress reduced the interaction between FOXO3a and HDAC2, leading to an increased histone H4K16 acetylation level in the p21 promoter region and upregulated p21 expression in a manner independent of p53 or E2F1. Phosphorylation of HDAC2 at Ser 394 is important for the HDAC2– FOXO3a interaction, and we found that cerebral ischemia/reperfusion reduced phosphorylation of HDAC2 at Ser 394 and mitigated the HDAC2–FOXO3a interaction in mouse brain tissue. Our study reveals the novel regulation of FOXO3a-mediated selective gene transcription via epigenetic modification in the process of oxidative stress-induced cell death, which could be exploited therapeutically. © 2015 the authors.
Xu D.,CAS Institute of Genetics and Developmental Biology |
Zhang F.,CAS Institute of Genetics and Developmental Biology |
Wang Y.,CAS Institute of Genetics and Developmental Biology |
Sun Y.,CAS Institute of Genetics and Developmental Biology |
And 2 more authors.
Cell Reports | Year: 2014
Mutations of WD40-repeat protein 62 (WDR62) have been identified recently to cause human MCPH (autosomal-recessive primary microcephaly), a neurodevelopmental disorder characterized by decreased brain size. However, the underlying mechanism is unclear. Here, we investigate the function of WDR62 in brain development and the pathological role of WDR62 mutations. We find that WDR62 knockdown leads to premature differentiation of neural progenitor cells (NPCs). The defect can be rescued by wild-type human WDR62, but not by the five MCPH-associated WDR62 mutants. We demonstrate that WDR62 acts upstream of JNK signaling in the control of neurogenesis. Depletion of JNK1 and WDR62 incurs very similar defects including abnormal spindle formation and mitotic division of NPCs as well as premature NPC differentiation during cortical development. Thus, our findings indicate that WDR62 is required for proper neurogenesis via JNK1 and provide an insight into the molecular mechanisms underlying MCPH pathogenesis. © 2014 The Authors.
Qiu X.,CAS Institute of Biophysics |
Qiu X.,University of Chinese Academy of Sciences |
Zhu Q.,CAS Institute of Biophysics |
Zhu Q.,University of Chinese Academy of Sciences |
And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Vesiclerecycling is pivotal for maintaining reliable synaptic signaling, but its basic properties remain poorly understood. Here, we developed an approach to quantitatively analyze the kinetics of vesicle recyclingwith exquisite signal and temporal resolution at the calyx of Held synapse. The combination of this electrophysiological approach with electron microscopy revealed that ∼80% of vesicles (∼270,000 out of ∼330,000) in the nerve terminal are involved in recycling. Under sustained stimulation, recycled vesicles start to be reused in tens of seconds when ∼47% of the preserved vesicles in the recycling pool (RP) are depleted. The heterogeneity of vesicle recycling as well as two kinetic components of RP depletion revealed the existence of a replenishable pool of vesicles before the priming stage and led to a realistic kinetic model that assesses the size of the subpools of the RP. Thus, our study quantified the kinetics of vesicle recycling and kinetically dissected the whole vesicle pool in the calyceal terminal into the readily releasable pool (∼0.6%), the readily priming pool (∼46%), the premature pool (∼33%), and the resting pool (∼20%). © 2015, National Academy of Sciences. All rights reserved.
Beijing Neurosurgical Institute and Beijing Institute For Brain Disorders | Date: 2015-07-15
The present invention provides an artificial synthetic cDNA (complementary deoxyribonucleic acid). The said artificial synthetic cDNA encodes a fused protein which is specifically presented in secondary glioblastoma, and the said artificial synthetic cDNA can be used as a biomarker for detecting the secondary glioblastoma. The present invention further provides a method for detecting secondary glioblastoma. According to the above technical solutions, the accuracy in distinguishing the secondary glioblastoma from primary glioblastoma is effectively improved in the present invention.