ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Cell-autonomous and non-cell-autonomous neuroprotective functions of RORα in neurons and astrocytes during hypoxia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Hypoxia-inducible factor-1: A new neuroprotective agent for the treatment of hyperglycemia after stroke.Neural regeneration research · 2026Article
- Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.Investigative ophthalmology & visual science · 2025Article
- The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Unravelling the link between circadian clock genes and brain tumors: From pathological disruptions to potential therapeutic interventions.Frontiers in pharmacology · 2025Review
- Neuroprotective role for RORA in Parkinson's disease revealed by analysis of post-mortem brain and a dopaminergic cell line.NPJ Parkinson's disease · 2023Article
- Circadian Control of Glial Cell Homeodynamics.Journal of biological rhythms · 2022Article
- Circadian stabilization loop: the regulatory hub and therapeutic target promoting circadian resilience and physiological health.F1000Research · 2022Review
- Glial Cell Line-Derived Neurotrophic Factor and Focal Ischemic Stroke.Neurochemical research · 2021Review
- GLAST-CreERGlia · 2020Article
- Loss of RAR-related orphan receptor alpha (RORα) selectively lowers docosahexaenoic acid in developing cerebellum.Prostaglandins, leukotrienes, and essential fatty acids · 2020Article
- Retinoid receptor-related orphan receptor alpha: a key gene setting brain circuits.Neural regeneration research · 2018Article
- Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.Gene expression patterns : GEP · 2016Article
- Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism.Molecular autism · 2015Article
- Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD.Frontiers in psychiatry · 2013Article
- RORalpha, a key to the development and functioning of the brain.Cerebellum (London, England) · 2012Review
- Neuronal responses to physiological stress.Frontiers in genetics · 2012Article
- Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism.Nuclear receptor researchArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is increasing evidence to suggest that the neuronal response to hypoxia is regulated through their interactions with astrocytes. However, the hypoxia-induced molecular mechanisms within astrocytes which influence neuronal death have yet to be characterized. In this study, we investigated the roles of the nuclear receptor RORα (retinoid-related orphan receptor-α) respectively in neurons and astrocytes during hypoxia using cultures and cocultures of neurons and astrocytes obtained from RORα-deficient mice. We found that loss of RORα function in neuronal cultures increases neuronal death after hypoxia, suggesting a cell-autonomous neuroprotective effect of RORα. Moreover, wild-type neurons cocultured with RORα-deficient astrocytes are characterized by a higher death rate after hypoxia than neurons cocultured with wild-type astrocytes, suggesting that RORα also has a non-cell-autonomous action. By using cocultures of neurons and astrocytes of different genotypes, we showed that this neuroprotective effect of RORα in astrocytes is additive to its effect in neurons, and is mediated in part by cell-to-cell interactions between neurons and astrocytes. We also found that RORα is upregulated by hypoxia in both neurons and astrocytes. Furthermore, our data showed that RORα does not alter oxidative mechanisms during hypoxia but regulates hypoxic inducible factor 1α (HIF-1α) expression, a major regulator of hypoxia sensing, in a cell-specific manner. Indeed, the neuroprotective function of RORα in astrocytes correlates with a downregulation of HIF-1α selectively in these cells. Altogether, our results show that RORα is a key molecular player in hypoxia, protecting neurons through its dual action in neurons and astrocytes.
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