Potential Roles of Mitochondria-Associated ER Membranes (MAMs) in Traumatic Brain Injury

Sun, Dongdong; Chen, Xin; Gu, Gang; Wang, Jianhao; Zhang, Jianning

doi:10.1007/s10571-017-0484-2

Cited by 28 publications

(20 citation statements)

References 94 publications

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“…Along with the evidence that miR-132/212 was consistently downregulated in AD [24], it is reasonable to speculate that miR-212 may act like a bridge between TBI and neurodegenerative diseases. Moreover, there is a consensus that crosstalk widely exists between ferroptosis and other forms of regulated cell death [53,[63][64][65][66], and emerging evidence indicates that miR-212 may prevent neuron death by inhibiting other target genes, like Sirt2 [67] or participating in other pathways, like autophagy [65,66] or apoptosis [63]. Further studies are urgently required to identify whether miR-212-5p is involved in any other pathologic process of TBI.…”

Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

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Ferroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). MiR-212-5p has previously been reported to be downregulated in extracellular vesicles following TBI. To investigate whether miR-212-5p is involved in the ferroptotic neuronal death in TBI mice, we first examined the accumulation of malondialdehyde (MDA) and ferrous ion, and the expression of ferroptosis-related molecules at 6 h, 12 h, 24 h, 48 h and 72 h following controlled cortical impact (CCI) in mice. There was a significant upregulation in the expression of Gpx4 and Acsl4 at 6 h, Slc7a11 from 12 h to 72 h, and Nox2 and Sat1 from 6 h to 72 h post injury. Similarly, an upregulation in the expression of Gpx4 at 6 h, Nox2 from 6 h to 72 h, xCT from 12 h to 72 h, and Sat1 at 72 h after CCI was observed at the protein level. Interestingly, MDA and ferrous ion were increased whereas miR-212-5p was decreased in the CCI group compared to the sham group. Furthermore, we found that overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. In addition, administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. Collectively, these findings indicate that miR-212-5p may protect against ferroptotic neuronal death in CCI mice partially by targeting Ptgs2.

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Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

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“…The TBI-induced neuronal death has been commonly delineated into two different categories: necrosis in the primary phase and apoptosis in the secondary phase. There are many forms of apoptosis, such as intrinsic apoptosis, extrinsic apoptosis, mitochondrial apoptosis, endoplasmic reticulum (ER)-associated apoptosis, and the iron-related apoptosis (ferroptosis), all of which can be observed be used as therapeutic target after TBI 5,6 . In addition, necroptosis, a recently discovered form of necrosis, is demonstrated to be a programmed cell death and participates in secondary neuronal cell death after TBI 7 .…”

Section: Introductionmentioning

confidence: 99%

Arc silence aggravates traumatic neuronal injury via mGluR1-mediated ER stress and necroptosis

et al. 2020

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Delayed neuronal death is associated with neurological deficits and mortality after traumatic brain injury (TBI), where post-synaptic density (PSD) proteins are thought to play key roles. The immediate-early gene (IEG) coded protein Arc is a brain-specific PSD protein that controls synaptic plasticity and learning behaviors. In this study, we investigated the expression and biological function of Arc in neuronal death after TBI in an in vitro model mimicked by traumatic neuronal injury (TNI) in cortical neurons. TNI caused a temporal increase of Arc expression at 3 and 6 h. Knockdown of Arc expression using small interfering RNA (Si-Arc-3) promoted TNI-induced cytotoxicity and apoptosis. The results of western blot showed that Si-Arc-3 transfection further enhanced the activation of endoplasmic reticulum (ER) stressassociated factors, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 after TNI. In addition, knockdown of Arc significantly increased expression of (receptor-interacting protein kinase 1) RIP1 and the number of necroptotic cells, which were apparently prevented by necrostatin-1 (Nec-1). The results of immunostaining and western blot showed that knockdown of Arc activated the metabotropic glutamate receptor 1 (mGluR1) and intracellular Ca 2+ release in neurons. Mechanistically, the Si-Arc-3-induced activation of ER stressassociated factors, RIP1 expression, apoptosis, and necroptosis were partially reversed by the mGluR1 antagonist AIDA. In summary, our data suggest that silence of Arc expression aggravates neuronal death after TNI by promoting apoptosis and necroptosis. These data support for the first time that Arc may represent a novel candidate for therapies against TBI.

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“…Although the mechanism of TBI is unclear, several previous studies have demonstrated the involvement of oxidative stress and apoptosis (Cheng et al, 2016;Liu et al, 2018). Several signaling pathways are involved in regulating oxidative stress after TBI (Sun et al, 2017;Fu et al, 2018). Nrf2 signaling pathway is activated after oxidative stress to regulate downstream target genes, such as HO1 (Hall et al, 2018;Zhang and Wang, 2018).…”

Section: Introductionmentioning

confidence: 99%

β-carotene provides neuroprotection after experimental traumatic brain injury via the Nrf2-ARE pathway

Chen

Gao

et al. 2019

J. Integr. Neurosci.

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J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c eThis is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/)We investigate whether β -carotene, a known natural antioxidant, can reduce oxidative stress induced by traumatic brain injury. In addition, we investigated the underlying mechanism of traumatic brain injury focusing on the NF-E2-related factor (Nrf2) pathway. A controlled cortical impact model was used to mimic traumatic brain injury. Using this model, we evaluated brain edema, lesion volume, neurologic deficits, reactive oxygen species, and the expression of Nrf2-related protein markers. The results of our study demonstrated that cognitive performance and neural functions were improved with β -carotene administration. In addition, β -carotene reduced brain edema and reactive oxygen species levels after traumatic brain injury. Nrf2 nuclear accumulation was increased and was accompanied by decreased Keap1 expression. The expression of quinone oxidoreductase 1, a target gene of the Nrf2 signaling pathway was increased. However, lesion volume was not significantly reduced after β -carotene treatment. Taken together, our data demonstrated that β -carotene administration was neuroprotective and alleviated oxidative stress by modulating the Nrf2/Keap1mediated antioxidant pathway in the traumatic brain injury model. KeywordsTraumatic brain injury; β -carotene; oxidative stress; Nrf2-ARC signaling pathway; mouse model 154Chen et al. 156Chen et al.

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Potential Roles of Mitochondria-Associated ER Membranes (MAMs) in Traumatic Brain Injury

Cited by 28 publications

References 94 publications

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

Arc silence aggravates traumatic neuronal injury via mGluR1-mediated ER stress and necroptosis

β-carotene provides neuroprotection after experimental traumatic brain injury via the Nrf2-ARE pathway

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