ArticleJournal of neurochemistry2015
The mechanistic target of rapamycin (mTOR) pathway and S6 Kinase mediate diazoxide preconditioning in primary rat cortical neurons.
Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Candidate Mechanisms of Cerebral Ischemia/Hypoxia Tolerance: Insights from Hibernating Rodents.Neurochemical research · 2026Review
- Closed-loop rehabilitation of upper-limb dyskinesia after stroke: from natural motion to neuronal microfluidics.Journal of neuroengineering and rehabilitation · 2025Review
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Three-dimensional object geometry of mitochondria-associated signal: 3-D analysis pipeline for two-photon image stacks of cerebrovascular endothelial mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Article
- Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.EMBO reports · 2023Article
- Detrimental effects of transient cerebral ischemia on middle cerebral artery mitochondria in female rats.American journal of physiology. Heart and circulatory physiology · 2022Article
- Dysregulation of mTOR Signaling after Brain Ischemia.International journal of molecular sciences · 2022Review
- Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning.Frontiers in genetics · 2020Review
- Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's disease and vascular cognitive impairment.American journal of physiology. Heart and circulatory physiology · 2018Article
- Role of mTORC1 Controlling Proteostasis after Brain Ischemia.Frontiers in neuroscience · 2018Review
- Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.Comprehensive Physiology · 2016Review
- Depolarization of mitochondria in neurons promotes activation of nitric oxide synthase and generation of nitric oxide.American journal of physiology. Heart and circulatory physiology · 2016Article
- Vascular mTOR-dependent mechanisms linking the control of aging to Alzheimer's disease.Biochimica et biophysica acta · 2016Review
- A novel quantitative high-throughput screen identifies drugs that both activate SUMO conjugation via the inhibition of microRNAs 182 and 183 and facilitate neuroprotection in a model of oxygen and glucose deprivation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- HRP-3 protects the hepatoma cells from glucose deprivation-induced apoptosis.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We examined the role of the mechanistic target of rapamycin (mTOR) pathway in delayed diazoxide (DZ)-induced preconditioning of cultured rat primary cortical neurons. Neurons were treated for 3 days with 500 μM DZ or feeding medium and then exposed to 3 h of continuous normoxia in Dulbecco's modified eagle medium with glucose or with 3 h of oxygen-glucose deprivation (OGD) followed by normoxia and feeding medium. The OGD decreased viability by 50%, depolarized mitochondria, and reduced mitochondrial respiration, whereas DZ treatment improved viability and mitochondrial respiration, and suppressed reactive oxygen species production, but did not restore mitochondrial membrane potential after OGD. Neuroprotection by DZ was associated with increased phosphorylation of protein kinase B (Akt), mTOR, and the major mTOR downstream substrate, S6 Kinase (S6K). The mTOR inhibitors rapamycin and Torin-1, as well as S6K-targeted siRNA abolished the protective effects of DZ. The effects of DZ on mitochondrial membrane potential and reactive oxygen species production were not affected by rapamycin. Preconditioning with DZ also changed mitochondrial and non-mitochondrial oxygen consumption rates. We conclude that in addition to reducing reactive oxygen species (ROS) production and mitochondrial membrane depolarization, DZ protects against OGD by activation of the Akt-mTOR-S6K pathway and by changes in mitochondrial respiration. Ischemic strokes have limited therapeutic options. Diazoxide (DZ) preconditioning can reduce neuronal damage. Using oxygen-glucose deprivation (OGD), we studied Akt/mTOR/S6K signaling and mitochondrial respiration in neuronal preconditioning. We found DZ protects neurons against OGD via the Akt/mTOR/S6K pathway and alters the mitochondrial and non-mitochondrial oxygen consumption rate. This suggests that the Akt/mTOR/S6k pathway and mitochondria are novel stroke targets.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.