ArticleNeurobiology of disease2011
Presynaptic silencing is an endogenous neuroprotectant during excitotoxic insults.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 26 citations in OpenAlex.
- Dopaminergic tone inhibits spontaneous glutamate release and augments homeostatic synaptic plasticity.Molecular psychiatry · 2026Article
- Article
- GABAeLife · 2023Article
- Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies.International journal of molecular sciences · 2022Review
- Molecular, Structural, Functional, and Pharmacological Sites for Vesicular Glutamate Transporter Regulation.Molecular neurobiology · 2020Review
- Cell Clearing Systems Bridging Neuro-Immunity and Synaptic Plasticity.International journal of molecular sciences · 2019Review
- The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation.PLoS biology · 2019Article
- Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- 24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2016Review
- Regulation of density of functional presynaptic terminals by local energy supply.Molecular brain · 2015Article
- Molecular mechanisms driving homeostatic plasticity of neurotransmitter release.Frontiers in cellular neuroscience · 2013Review
- Indistinguishable synaptic pharmacodynamics of the N-methyl-D-aspartate receptor channel blockers memantine and ketamine.Molecular pharmacology · 2013Article
- Astrocyte-derived thrombospondins mediate the development of hippocampal presynaptic plasticity in vitro.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Anesthetic protection of neurons injured by hypothermia and rewarming: roles of intracellular Ca2+ and excitotoxicity.Anesthesiology · 2012Article
- Presynaptically silent synapses: dormancy and awakening of presynaptic vesicle release.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2012Review
- Synaptic NMDA receptors mediate hypoxic excitotoxic death.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.PloS one · 2012Article
- Differential requirement for protein synthesis in presynaptic unmuting and muting in hippocampal glutamate terminals.PloS one · 2012Article
- Excitotoxicity triggered by Neurobasal culture medium.PloS one · 2011Article
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
Glutamate release is a root cause of acute and delayed neuronal damage in response to hypoxic/ischemic insults. Nevertheless, therapeutics that target the postsynaptic compartment have been disappointing clinically. Here we explored whether presynaptic silencing (muting) of glutamatergic terminals is sufficient to reduce excitotoxic damage resulting from hypoxia and oxygen/glucose deprivation. Our evidence suggests that strong depolarization, previously shown to mute glutamate synapses, protects neurons by a presynaptic mechanism that is sensitive to inhibition of the proteasome. Postsynaptic Ca2+ rises in response to glutamate application and toxicity in response to exogenous glutamate treatment were unaffected by depolarization preconditioning. These features strongly suggest that reduced glutamate release explains preconditioning protection. We addressed whether hypoxic depolarization itself induces presynaptic silencing, thereby participating in the damage threshold for hypoxic insult. Indeed, we found that the hypoxic insult increased the percentage of mute glutamate synapses in a proteasome-dependent manner. Furthermore, proteasome inhibition exacerbated neuronal loss to mild hypoxia and prevented hypoxia-induced muting. In total our results suggest that presynaptic silencing is an endogenous neuroprotective mechanism that could be exploited to reduce damage from insults involving excess synaptic glutamate release.
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.