ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Chronic stress exacerbates tau pathology, neurodegeneration, and cognitive performance through a corticotropin-releasing factor receptor-dependent mechanism in a transgenic mouse model of tauopathy.
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 144 papers.
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144 citing papers in PubMed, 260 citations in OpenAlex.
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- Tracking the Continuous Time Dynamics of Tau and Depressive Symptoms across the Alzheimer's Disease Continuum.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Maternal Traumatic Brain Injury Increases Fetal Brain Cis p-tau Levels: Evidence for Potential Transplacental Effects in a Murine Model.Journal of molecular neuroscience : MN · 2026Article
- tRNA-derived fragments elevated in Alzheimer's disease promote Tau aggregation.bioRxiv : the preprint server for biology · 2026Article
- The Amygdala and Politics.Brain sciences · 2026Review
- Evaluating the impact of intracerebroventricular norepinephrine on spatial memory in rats: Insights into sporadic Alzheimer's pathogenesis.IBRO neuroscience reports · 2026Article
- Age-dependent alterations of TRPA1 and urocortin 1 signaling in the Edinger-Westphal nucleus in a mouse model of Alzheimer's disease.Scientific reports · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Dapagliflozin mitigates cognitive deficits in a rat model of chronic restrained stress by addressing insulin resistance and mitochondrial dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Chronic social isolation-unpredictable stress induces early-onset cognitive deficits and exacerbates Aβ accumulation in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2025Article
- Mid-life exposure to chronic stress accelerates cerebrovascular dysfunction and upregulates oxidative stress in Alzheimer's disease mice.Journal of Alzheimer's disease : JAD · 2025Article
- Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise.Journal of neurochemistry · 2025Review
- Altered Functional Connectivity and Amyloid Deposition in Posttraumatic Stress Disorder-Associated Cognitive Impairment.AJNR. American journal of neuroradiology · 2025Article
- Hippocampal CA1 neuron, a crucial regulator for chronic stress exacerbating Alzheimer's disease progression.Cell & bioscience · 2025Article
- Long-term exposure to excessive norepinephrine in the brain induces tau aggregation, neuronal death, and cognitive deficits in early tau transgenic mice.Aging cell · 2025Article
- Research progress on plant-derived natural compounds regulating the MAPK signaling pathway for the prevention and therapy of Alzheimer's disease.Frontiers in pharmacology · 2025Review
- Cerebral amyloid angiopathy: a narrative review.Frontiers in aging neuroscience · 2025Review
- The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease.International journal of molecular sciences · 2024Review
- The multiple roles of chronic stress and glucocorticoids in Alzheimer's disease pathogenesis.Trends in neurosciences · 2024Review
84 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Because overactivation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in Alzheimer's disease (AD), dysregulation of stress neuromediators may play a mechanistic role in the pathophysiology of AD. However, the effects of stress on tau phosphorylation are poorly understood, and the relationship between corticosterone and corticotropin-releasing factor (CRF) on both β-amyloid (Aβ) and tau pathology remain unclear. Therefore, we first established a model of chronic stress, which exacerbates Aβ accumulation in Tg2576 mice and then extended this stress paradigm to a tau transgenic mouse model with the P301S mutation (PS19) that displays tau hyperphosphorylation, insoluble tau inclusions and neurodegeneration. We show for the first time that both Tg2576 and PS19 mice demonstrate a heightened HPA stress profile in the unstressed state. In Tg2576 mice, 1 month of restraint/isolation (RI) stress increased Aβ levels, suppressed microglial activation, and worsened spatial and fear memory compared with nonstressed mice. In PS19 mice, RI stress promoted tau hyperphosphorylation, insoluble tau aggregation, neurodegeneration, and fear-memory impairments. These effects were not mimicked by chronic corticosterone administration but were prevented by pre-stress administration of a CRF receptor type 1 (CRF(1)) antagonist. The role for a CRF(1)-dependent mechanism was further supported by the finding that mice overexpressing CRF had increased hyperphosphorylated tau compared with wild-type littermates. Together, these results implicate HPA dysregulation in AD neuropathogenesis and suggest that prolonged stress may increase Aβ and tau hyperphosphorylation. These studies also implicate CRF in AD pathophysiology and suggest that pharmacological manipulation of this neuropeptide may be a potential therapeutic strategy for AD.
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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.