ArticleExperimental gerontology2020
Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits.
Article in Experimental gerontology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Oligodendrocyte dysfunction in human age-related cognitive decline.Nature medicine · 2026Article
- Review
- Hyperbaric oxygen preconditioning alleviates spinal cord injury by inhibiting pro-inflammatory astrocyte polarization in a rat model of decompression sickness.Frontiers in immunology · 2026Article
- Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders.Molecular neurobiology · 2025Review
- Phytochemical Profiling and Anti-Obesogenic Potential ofMolecules (Basel, Switzerland) · 2025Article
- Development and validation of a machine learning-based risk prediction model for post-stroke cognitive impairment.Scientific reports · 2025Article
- Epigenetic Dysregulation in Neurodegenerative Disease: Implications for Neuropathology and Therapy.Cureus · 2025Review
- Nrf2 Ameliorates Sevoflurane-Induced Cognitive Deficits in Aged Mice by Inhibiting Neuroinflammation in the Hippocampus.Molecular neurobiology · 2025Article
- Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases.Cells · 2025Review
- The Emerging Role of Brain Mitochondria in Fear and Anxiety.Current topics in behavioral neurosciences · 2025Review
- Role of Nrf2 in Oxidative Stress, Neuroinflammation and Autophagy in Alzheimer's Disease: Regulation of Nrf2 by Different Signaling Pathways.Current molecular medicine · 2025Review
- Multitarget Effects of Nrf2 Signalling in the Brain: Common and Specific Functions in Different Cell Types.Antioxidants (Basel, Switzerland) · 2024Review
- Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice.International journal of molecular sciences · 2024Article
- Neuronal Senescence in the Aged Brain.Aging and disease · 2023Review
- Effect of Nrf2 loss on senescence and cognition of tau-based P301S mice.GeroScience · 2023Article
- Review
- The Interaction ofCells · 2022Review
- TAZ ameliorates the microglia-mediated inflammatory response via the Nrf2-ROS-NF-κB pathway.Molecular therapy. Nucleic acids · 2022Article
- Article
- Activation of α7 Nicotinic Acetylcholine Receptor by its Selective Agonist Improved Learning and Memory of Amyloid Precursor Protein/Presenilin 1 (APP/PS1) Mice via the Nrf2/HO-1 Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) regulates cellular bioenergetics and improves neuronal health in aging. Yet how NRF2 participates in maintaining synaptic, mitochondrial and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects neuronal metabolism, synaptic density and cognitive performance in aged mice. Dendritic arborization as well as synaptic and mitochondrial gene expression was evaluated in hippocampal neurons isolated from mice lacking NRF2 (NRF2KO) and from wild-type (WT) C57BL6 mice. Mitochondrial function of these neurons was evaluated using the Seahorse XF platform. Additionally learning, memory and executive function were assessed in 20 month old NRF2KO and age-matched WT mice using conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) tests. Hippocampal bioenergetics was profiled using mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial and synaptic genes. NRF2KO neurons had reduced dendritic complexity and diminished synaptic gene expression. This was accompanied by impaired mitochondrial function and decreased mitochondrial gene expression. Similar mitochondrial deficits were observed in the brains of aged NRF2KO mice. These animals also had significantly impaired cognitive performance and reduced synaptic gene expression as well. These data point to a role for NRF2 in maintaining mitochondrial and cognitive function during aging and suggest that the transcription factor may be a viable target for cognitive enhancing interventions. Because mitochondrial dysfunction and cognitive impairment also occur together in many neurodegenerative conditions there may be broad therapeutic potential of NRF2 activating agents.
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