Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling

Li, Xigong; Du, Junhua; Yang, Lu; Lin, Xiang

doi:10.4103/1673-5374.247476

Cited by 37 publications

(23 citation statements)

References 50 publications

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“…At 12 h post-modeling, rats ( n = 3, at each group) were deeply anesthetized with 4% sodium pentobarbital (50 mg/kg, i.p.). Then, they were perfused transcardially with normal saline, followed by 4% buffered paraformaldehyde (Servicebio G1101, China), and until the right atrium flowed out clear paraformaldehyde and the lungs turned white ( Li et al, 2019 ; Yin et al, 2019 ). The spinal cords from L4 to L6 were removed rapidly for analysis because of their vulnerability to ischemic injury ( Li et al, 2014a ).…”

Section: Methodsmentioning

confidence: 99%

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

et al. 2020

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BackgroundNeuroinflammation and cellular apoptosis caused by spinal cord ischemia/reperfusion (I/R) injury result in neurological dysfunction. MicroRNAs (miRs) have crucial functions in spinal cord I/R injury pathogenesis according to previous evidences. Herein, whether miR-128-3p contributes to spinal cord I/R injury by regulating specificity protein 1 (SP1) was assessed.MethodsA rat model of spinal cord I/R injury was established by occluding the aortic arch for 14 min. Then, miR-128-3p’s interaction with SP1 was detected by dual-luciferase reporter assays. Next, miR-128-3p mimic and inhibitor, as well as adenovirus-delivered shRNA specific for SP1 were injected intrathecally for assessing the effects of miR-128-3p and SP1 on rats with spinal cord I/R injury. SP1, Bax and Bcl-2 expression levels in I/R injured spinal cord tissues were evaluated by Western blotting, while IL-1β, TNF-α, and IL-6 were quantitated by ELISA. Tarlov scores were obtained to detect hind-limb motor function. Evans blue (EB) dye extravasation was utilized to examine blood–spinal cord barrier (BSCB) permeability. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining was performed for neuronal apoptosis assessment.ResultsMiR-128-3p expression was decreased, while SP1 amounts were increased in rat spinal cord tissue specimens following I/R. SP1 was identified as a miR-128-3p target and downregulated by miR-128-3p. MiR-128-3p overexpression or SP1 silencing alleviated I/R-induced neuroinflammation and cell apoptosis, and improved Tarlov scores, whereas pretreatment with miR-128-3p inhibitor aggravated the above injuries.ConclusionOverexpression of miR-128-3p protects neurons from neuroinflammation and apoptosis during spinal cord I/R injury partially by downregulating SP1.

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Section: Methodsmentioning

confidence: 99%

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

et al. 2020

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“…However, during the stage of neuropathy, mTOR signaling pathway could be offering an interesting target based on its neuroprotective effects, as depicted in many studies where PI3K/Akt/mTOR signaling activation affords neuroprotection. This is shown in traumatic brain injury rat model (Shen et al, 2017), in brain ischemia models (Lee et al, 2016) or in spinal cord injury (Li et al, 2019; Walker et al, 2019). This neuroprotective effect is regulated via its role in the balance between autophagy and apoptosis (Nguyen et al, 2010).…”

Section: Discussionmentioning

confidence: 92%

Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation

et al. 2019

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Aim: Diabetic retinopathy causes loss of vision in adults at working-age. Few therapeutic options are available for treatment of diabetic retinopathy. Carbamazepine (CARB), a widely used antiepileptic drug, was recently accounted for its neuroprotective effect. Nerve growth factor (NGF) activates various cascades among which, PI3K/Akt/mTOR pathway has a vital action in NGF-mediated neuronal differentiation and survival. This study evaluated the effect of CARB in the treatment of diabetic retina and unveiled some of the underlying molecular mechanisms.Main Methods: Alloxan diabetes model was induced in 36 albino well-acclimatized mice. After establishment of the diabetic model in 9 weeks, mice were assigned to treatment groups: (1) saline, (2) alloxan-diabetic, (3 and 4) alloxan+CARB (25 or 50 mg per kg p.o) for 4 weeks. After completion of the therapeutic period, mice were sacrificed and eyeballs were enucleated. Retinal levels of NGF and PI3K/Akt were assessed using real-time polymerase chain reaction. Further, total and phosphorylated TrKA, PI3K, Akt, mTOR as well as Caspase-3 were measured by Western blot analysis.Key Findings: Histopathological examination demonstrated that CARB attenuated vacuolization and restored normal thickness and organization of retinal cell layers. In addition, CARB increased pTrKA/TrKA ratio and ameliorated diabetes-induced reduction of NGF mRNA and immunostaining in retina. Additionally, it augmented the mRNA expression of PI3K and Akt, as well as the protein level of the phosphorylated PI3/Akt/mTOR.Significance: Results highlighted, for the first time, the neuronal protective effect for CARB in diabetic retina, which is mediated, at least in part, by activation of the NGF/PI3K/Akt/mTOR pathway.

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“…In these cases, the mTOR inhibition seems to be a reasonable strategy for treating brain pathologies. Previous studies of several models of neurodegenerative disorders have demonstrated that neuroprotective actions of mTOR inhibitors can be a result from the activation of autophagic processes and lysosomal biogenesis [ 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

De Novo Transcriptome Profiling of Brain Tissue from the Annual Killifish Nothobranchius guentheri

Guvatova

Fedorova

Vershinina

et al. 2021

Life

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Nothobranchius is a genus of small annual killifish found in Africa. Due to the relatively short lifespan, as well as easy breeding and care, Nothobranchius fish are becoming widely used as a vertebrate model system. Studying the genome and transcriptome of these fish is essential for advancing the field. In this study, we performed de novo transcriptome assembly of brain tissues from Nothobranchius guentheri using Trinity. Annotation of 104,271 potential genes (with transcripts longer than 500 bp) was carried out; for 24,967 genes (53,654 transcripts), in which at least one GO annotation was derived. We also analyzed the effect of a long-term food supplement with Torin 2, second-generation ATP-competitive inhibitor of mTOR, on the gene expression changes in brain tissue of adult N. guentheri. Overall, 1491 genes in females and 249 genes in males were differently expressed under Torin 2-supplemented diet. According to the Gene Set Enrichment Analysis (GSEA), the majority of identified genes were predominantly involved in the regulation of metabolic process, dendritic spine maintenance, circadian rhythms, retrotransposition, and immune response. Thus, we have provided the first transcriptome assembly and assessed the differential gene expression in response to exposure to Torin 2, which allow a better understanding of molecular changes in the brain tissues of adult fish in the mTOR pathway inhibition.

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Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling

Cited by 37 publications

References 50 publications

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation

De Novo Transcriptome Profiling of Brain Tissue from the Annual Killifish Nothobranchius guentheri

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