ArticleMedical science monitor : international medical journal of experimental and clinical research2018
Downregulated Nuclear Factor E2-Related Factor 2 (Nrf2) Aggravates Cognitive Impairments via Neuroinflammation and Synaptic Plasticity in the Senescence-Accelerated Mouse Prone 8 (SAMP8) Mouse: A Model of Accelerated Senescence.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effect of dietary phytochemicals on nuclear factor erythroid 2-related factor 2 (Nrf2) activation: a systematic review of human intervention trials.Molecular biology reports · 2021Pooled it
- The REDOX balance in the prefrontal cortex is positively modulated by aerobic exercise and altered by overfeeding.Scientific reports · 2025Article
- Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment.Molecular neurobiology · 2024Review
- The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities.Biomolecules · 2023Review
- Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice.International journal of molecular sciences · 2022Article
- Physical-Exercise-Induced Antioxidant Effects on the Brain and Skeletal Muscle.Antioxidants (Basel, Switzerland) · 2022Review
- MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer’s disease in vivo and in vitroActa biochimica et biophysica Sinica · 2022Article
- Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging.Neurobiology of aging · 2021Article
- Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations.International journal of molecular sciences · 2021Article
- Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits.Experimental gerontology · 2020Article
- Comparison of the Protective Effects of Ginsenosides Rb1 and Rg1 on Improving Cognitive Deficits in SAMP8 Mice Based on Anti-Neuroinflammation Mechanism.Frontiers in pharmacology · 2020Article
- Nrf2 drives oxidative stress-induced autophagy in nucleus pulposus cells via a Keap1/Nrf2/p62 feedback loop to protect intervertebral disc from degeneration.Cell death & disease · 2019Article
- Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
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7 authors.
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Abstract
BACKGROUND We observed the effects of nuclear factor E2-related factor 2 (Nrf2) downregulation via intrahippocampal injection of a lentiviral vector on cognition in senescence-accelerated mouse prone 8 (SAMP8) to investigate the role of the (Nrf2)/antioxidant response element (ARE) pathway in age-related changes. MATERIAL AND METHODS Control lentivirus and Nrf2-shRNA-lentivirus were separately injected into the hippocampus of 4-month-old SAMR1 and SAMP8 mice and then successfully downregulated Nrf2 expression in this brain region. Five months later, cognitive function tests, including the novel object test, the Morris water maze test, and the passive avoidance task were conducted. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunohistochemistry was performed to observe an inflammatory response. Presynaptic synapsin (SYN) were observed by immunofluorescence. We then determined the Nrf2-regulated, heme oxygenase-1 (HO-1), P65, postsynaptic density protein (PSD), and SYN protein levels. The ultrastructure of neurons and synapses in the hippocampal CA1 region was observed by transmission electron microscopy. RESULTS Aging led to a decline in cognitive function compared with SAMR1 mice and the Nrf2-shRNA-lentivirus further exacerbated the cognitive impairment in SAMP8 mice. Nrf2, HO-1, PSD, and SYN levels were significantly reduced (all P<0.05) but high levels of inflammation were detected in SAMP8 mice with low expression of Nrf2. Furthermore, neurons were vacuolated, the number of organelles decreased, and the number of synapses decreased. CONCLUSIONS Downregulation of Nrf2 suppressed the Nrf2/ARE pathway, activated oxidative stress and neuroinflammation, and accelerated cognitive impairment in SAMP8 mice. Downregulation of Nrf2 accelerates the aging process through neuroinflammation and synaptic plasticity.
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