scholarly journals IL-10 produces a dual effect on OGD-induced neuronal apoptosis of cultured cortical neurons via the NF-κB pathway

Aging ◽  
2019 ◽  
Vol 11 (23) ◽  
pp. 10796-10813 ◽  
Author(s):  
Hongbin Chen ◽  
Wei Lin ◽  
Peiqiang Lin ◽  
Mouwei Zheng ◽  
Yongxing Lai ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Dual Effect ◽  
Cultured Cortical Neurons

scholarly journals Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

2006 ◽  
Vol 175 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Yinghua Ma ◽  
Jianxue Li ◽  
Isaac Chiu ◽  
Yawen Wang ◽  
Jacob A. Sloane ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Negative Regulator ◽  
Toll Like Receptor ◽  
Neuronal Responses ◽  
Adaptive Immune ◽  
Cultured Cortical Neurons

Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR–NF-κB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity.

scholarly journals The Bacterial Enzyme Cas13 Interferes with Neurite Outgrowth from Cultured Cortical Neurons

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 262
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer
Keyword(s):  
Rna Editing ◽  
Cortical Neurons ◽  
High Efficiency ◽  
Primary Cultures ◽  
Cultured Neurons ◽  
Therapeutic Tool ◽  
Bacterial Enzyme ◽  
Rna Targeting ◽  
Cultured Cortical Neurons ◽  
New Generation

The CRISPR-Cas13 system based on a bacterial enzyme has been explored as a powerful new method for RNA manipulation. Due to the high efficiency and specificity of RNA editing/interference achieved by this system, it is currently being developed as a new therapeutic tool for the treatment of neurological and other diseases. However, the safety of this new generation of RNA therapies is still unclear. In this study, we constructed a vector expressing CRISPR-Cas13 under a constitutive neuron-specific promoter. CRISPR-Cas13 from Leptotrichia wadei was expressed in primary cultures of mouse cortical neurons. We found that the presence of CRISPR-Cas13 impedes the development of cultured neurons. These results show a neurotoxic action of Cas13 and call for more studies to test for and possibly mitigate the toxic effects of Cas13 enzymes in order to improve CRISPR-Cas13-based tools for RNA targeting.

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

Abstract 91: Remodeling After Stroke: The Recovering Brain Is Vulnerable To Lipoxygenase-dependent Semaphorin Signaling

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Anton Pekcec ◽  
Kazim Yigitkanli ◽  
Joo Eun Jung ◽  
Hulya Karatas ◽  
Eng H Lo ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Cortical Neurons ◽  
Second Messengers ◽  
Artery Occlusion ◽  
Tube Formation ◽  
Stroke Recovery ◽  
Experimental Stroke ◽  
Axon Extension ◽  
Cultured Cortical Neurons ◽  
Cerebral Artery Occlusion

Background and Purpose— Recovery from stroke is limited in part by an inhibitory environment in the post-ischemic brain, but factors preventing successful remodeling are not well known. We sought to investigate if signaling from the axon guidance molecule semaphorin 3A (Sema3A) via eicosanoid second messengers can contribute to this inhibitory environment, and if blocking the Sema3A pathway can provide a benefit following experimental stroke. Methods— Cultured cortical neurons from mice were treated with recombinant Sema3A, or with the eicosanoids 12-HETE and 12-HPETE. Neurons from ALOX15 knockout mice, and a human brain endothelial cell line, were treated similarly. The filament model of MCAO was used to induce experimental stroke in mice, in some of which Sema3A was injected stereotactically into the striatum. The 12/15-LOX inhibitor LOXBlock-1 was injected intraperitoneally one week after MCAO. Results— Expression levels of 12/15-lipoxygenase (12/15-LOX) were increased within two hours after exposure of primary neurons to 90nM recombinant Sema3A. Either Sema3A, or the 12/15-lipoxygenase (12/15-LOX) metabolites 12-HETE and 12-HPETE at 300nM, blocked axon extension in neurons compared to solvent controls, and decreased tube formation in endothelial cells. The Sema3A effect was reversed by inhibiting 12/15-LOX, and neurons derived from 12/15-LOX knockout mice were insensitive to Sema3A. Following middle cerebral artery occlusion to induce stroke in mice, immunohistochemistry showed both Sema3A and 12/15-LOX are increased in the cortex up to two weeks. To determine if a Sema3A-dependent damage pathway is activated following ischemia, we injected recombinant Sema3A into the striatum. Sema3A alone did not cause injury in normal brains. But when injected into post-ischemic brains, Sema3A increased cortical damage by 79%, and again this effect was reversed by 12/15-LOX inhibition. Administration of the 12/15-LOX inhibitor LOXBlock-1 7 days after transient MCAO increased vascularization in the infarcted and peri-infarct area one week later. Conclusions— Our findings suggest that blocking the semaphorin pathway may provide a novel therapeutic strategy to improve stroke recovery.

scholarly journals Bifemelane Protects Cultured Cortical Neurons Against N-Methyl-D-aspartate Receptor-Mediated Glutamate Cytotoxicity

1998 ◽  
Vol 76 (3) ◽  
pp. 313-316 ◽  
Author(s):  
Akinori Akaike ◽  
Takehiko Maeda ◽  
Toshiaki Kume ◽  
Satoshi Kaneko
Keyword(s):  
Cortical Neurons ◽  
Aspartate Receptor ◽  
Cultured Cortical Neurons

scholarly journals Self-amplified BDNF transcription is a regulatory system for synaptic maturation in cultured cortical neurons

2015 ◽  
Vol 91 ◽  
pp. 55-61 ◽  
Author(s):  
Shingo Nakajima ◽  
Tadahiro Numakawa ◽  
Naoki Adachi ◽  
Yoshiko Ooshima ◽  
Haruki Odaka ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory System ◽  
Cultured Cortical Neurons ◽  
Synaptic Maturation ◽  
Bdnf Transcription
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