The Serum SIRT1 Protein is Associated with the Severity of Injury and Neurological Recovery in Mice with Traumatic Spinal Cord Injury

Zhong, Guibin; Yang, Yanqiu; Huang, Xiaodong; Chen, Junling; Feng, Danni; Wei, Ke; Chen, Jianwei; Chen, Haihong

doi:10.1016/j.neuroscience.2021.06.025

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…The body is at high levels of autophagy in healthy states, and high levels of autophagy inhibit BV2 activation and maintain homeostasis, while the opposite is true when the body is damaged [13,36] . SIRT1 has been found to promote BV2 cell autophagy; for example, in Alzheimer's disease, upregulation of SIRT1 activates BV2 cell autophagy to suppress neuroin ammation [37] .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been shown that SIRT1 is highly expressed in CNS and BV2 cells [9] . In the short term after SCI, serum SIRT1 levels were elevated and had a therapeutic effect on injury, but in long-term injury, because of the severity of organism damage, resulting in a decrease in SIRT1 levels, a negative correlation between SIRT1 levels and SCI injury was detected, i.e., the lower the SIRT1 level, the more severe the injury [13] . Therefore, we speculate that increasing SIRT1 levels after long-term injury may be a new direction for the treatment of SCI.…”

Section: Introductionmentioning

confidence: 99%

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SIRT1 inhibits Smad3 acetylation by reducing Lnc CRNDE transcription and inhibits BV2 cell overactivation to promote SCI neurological repair

Chen,

Li,

et al. 2023

Preprint

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Methods We established a BV2 cell activation model by in vitro lipopolysaccharide (LPS) treatment and a rat SCI model according to physical injury. We used HE staining, Luxol solid blue staining and Nissl staining to observe the spinal cord structure, RT‒qPCR to detect SIRT1 mRNA and Lnc CRNDE expression, western blotting to detect SIRT1 protein, BV2 cell activation protein marker (Iba-1) and autophagy-related protein (LC3; Beclin-1; P62) expression, immunoprecipitation reaction to detect the relationship between Smad3 and SIRT1 binding, RNA binding protein immunoprecipitation (RIP) to detect the relationship between Smad3 and CRNDE, dual luciferase reporter gene to verify the transcriptional regulation of CRNDE by Smad3, and immunofluorescence staining to detect the coexpression of BV2 cell activation marker (Iba-1) and autophagy marker (P62). Results SIRT1 was expressed at low levels in SCI and LPS-treated BV2 cells from SCI rats. Overexpression of SIRT1 promoted BV2 cell autophagy, inhibited BV2 cell overactivation, alleviated the pathological conditions of spinal cord congestion, edema and structural damage after SCI, improved BBB scores, increased neuronal numbers and promoted myelin regeneration. SIRT1 could inhibit Lnc CRNDE transcription by reducing Smad3. SIRT1 inhibits Lnc CRNDE transcription by reducing Smad3 acetylation and inhibiting its nuclear localization. Overexpression of CRNDE reversed the protective effect on SCI exhibited by SIRT1, and knockdown of CRNDE inhibited BV2 cell overactivation and promoted SCI repair. Conclusion SIRT1 promotes SCI repair by reducing Smad3 acetylation and inhibiting its nuclear localization to suppress Lnc CRNDE transcription and inhibit BV2 cell overactivation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SIRT1 inhibits Smad3 acetylation by reducing Lnc CRNDE transcription and inhibits BV2 cell overactivation to promote SCI neurological repair

Chen,

Li,

et al. 2023

Preprint

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“…In addition, inhibition of SIRT1 significantly promoted apoptotic neuronal death after TBI [63]. Similarly, serum SIRT1 levels were found to be increased after traumatic spinal cord injury [65]. Rodent studies that are focusing on ischemic injury have also shown increased SIRT1 protein levels at 18, 24, 48 h, and 7 days after middle cerebral artery occlusion [38, 39].…”

Section: Discussionmentioning

confidence: 99%

Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice

et al. 2022

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The variability of severity in hypoxia ischemia (HI) induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0-6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci’s rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using RT-qPCR. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi, and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.

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“…The MASCIS Impactor, NYU Impactor II [ 28 ] (W.M. Keck Center for Collaborative Neuroscience, Rutgers the State University of New Jersey, America) was set to one of two forces (mild SCI group: 5 g × 10 mm; severe SCI group: 5 g × 40 mm) to generate a mild or severe SCI mouse model [ 13 ]. After surgery, the mice were allowed to recover on warm blankets.…”

Section: Methodsmentioning

confidence: 99%

“…In acute SCI models, Tau, S-100β, and NSE protein levels were found to be significantly increased [ 5 , [8] , [9] , [10] ]. The preliminary conclusion that serum NSE, serum albumin, and S-100β levels were correlated with the degree of spinal cord injury remains to be confirmed with a large sample size [ [11] , [12] , [13] , [14] ]. The serum level of the astrocyte marker GFAP is associated with neurological dysfunction and spinal cord edema after traumatic SCI and can be used as a diagnostic biomarker for the occurrence and severity of SCI in the acute injury phase but has limited reliability for clinical use [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Steroid inhibited Serpina3n expression which was positively correlated with the degrees of spinal cord injury

Chen,

Wu,

Zhang

et al. 2024

Heliyon

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The Serum SIRT1 Protein is Associated with the Severity of Injury and Neurological Recovery in Mice with Traumatic Spinal Cord Injury

Cited by 6 publications

References 36 publications

SIRT1 inhibits Smad3 acetylation by reducing Lnc CRNDE transcription and inhibits BV2 cell overactivation to promote SCI neurological repair

SIRT1 inhibits Smad3 acetylation by reducing Lnc CRNDE transcription and inhibits BV2 cell overactivation to promote SCI neurological repair

Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice

Steroid inhibited Serpina3n expression which was positively correlated with the degrees of spinal cord injury

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