CaMKII-Mediated CREB Phosphorylation Is Involved in Ca2+-Induced BDNF mRNA Transcription and Neurite Outgrowth Promoted by Electrical Stimulation

Yan, Xiaodong; Liu, Juanfang; Ye, Zhengxu; Huang, Jinghui; He, Fangping; Xiao, Wei; Hu, Xueyu; Luo, Zhuojing

doi:10.1371/journal.pone.0162784

Cited by 104 publications

(81 citation statements)

References 73 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ES alters the local electrical field [45], enhances the release of nerve growth factors from SCs [46], promotes the induction of neurotrophins release [15], and enhances the proliferation and functional activity of SCs in vitro. ES was shown to enhance the release of nerve growth factor and brain-derived neurotrophic factor from Schwann cells in a calcium-dependent mechanism [46]. However, the effect of ES on transplanted NCSCs remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

View full text Add to dashboard Cite

Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. Optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.

show abstract

Section: Discussionmentioning

confidence: 99%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

View full text Add to dashboard Cite

show abstract

“…ERKs are able to activate and transfer signals to the nucleus quickly, in order to induce CREB phosphorylation and activate the nuclear transcription factor, CREB. Enhanced CREB ultimately results in increased expression of BDNF (34). These data suggest a positive feedback loop between BDNF and CREB, which may be associated with nerve cell nutrition and nerve injury repair (35).…”

Section: Discussionmentioning

confidence: 99%

Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways

Dong

Wang

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS. In total, 24 male Wistar rats were randomly divided into three groups, including control (n=8, no treatment), induced with chronic unpredictable mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for cell survival and proliferation assays. In KXS rats, increased protein expression levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the hippocampus and prefrontal cortex, compared with the CMS model group. Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3β were also detected in the hippocampus and prefrontal cortex of KXS-treated rats compared with CMS model rats and in primary hippocampal neuronal cells treated with KXS. These results suggest that pCREB and upstream components, including TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect induced by KXS. Further studies are required to confirm these findings.

show abstract

“…BDNF promoted neurogenesis and protected against ischemic injury (Schabitz et al, 2007;Guan et al, 2012). Moreover, CREB phosphorylation promoted the BDNF transcription (Tao et al, 1998;Yan et al, 2016). Therefore, we analyzed the effect of thioperamide on BDNF levels.…”

Section: Discussionmentioning

confidence: 99%

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

Wang

Liu

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Chronic cerebral hypoperfusion (CCH) is a neurodegenerative disease, which induces cognitive impairments in the central nervous system (CNS). Histamine H3 receptor (H3R) is an autoreceptor involved in the modulation of neurogenesis and synaptic plasticity in the CNS. However, the role of H3R in CCH-induced injury and the related mechanisms remain to be clarified. Here, we found that thioperamide (THIO), a H3R antagonist, promotes the proliferation of NE-4C stem cells under either normal or oxygen-glucose deprivation (OGD) condition in vitro. Thioperamide promotes the phosphorylation of cAMP-response element binding (CREB), and thereby upregulates the expression and release of brain-derived neurotrophic factor (BDNF). However, H89, an inhibitor of protein kinase A (PKA)/CREB, reverses the effects of thioperamide on either BDNF expression and release or cell proliferation in NE-4C stem cells. Moreover, thioperamide has protective effects on OGDinduced impairment of cell viability and neuronal morphology in primary neurons in vitro. Furthermore, thioperamide enhanced neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ) regions in vivo, and ameliorated CCH-induced cognitive impairments. Taken together, these findings showed that thioperamide protects primary neurons against OGD-induced injury and promotes the proliferation of neural stem cells in DG and SVZ regions through CREB/BDNF pathways, thereby improving cognitive deficit.

show abstract

CaMKII-Mediated CREB Phosphorylation Is Involved in Ca2+-Induced BDNF mRNA Transcription and Neurite Outgrowth Promoted by Electrical Stimulation

Cited by 104 publications

References 73 publications

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

Contact Info

Product

Resources

About