ArticleJournal of neuroinflammation2025
Depression exacerbates AD pathology through lactate-dependent activation of microglial Kv1.3 to promote Aβ-containing exosome spreading.
Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Plasma neurofilament light chain and regional brain atrophy mediate the association of neuropsychiatric symptoms with cognition in Alzheimer's disease: evidence from two population-based studies.Psychological medicine · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Down-regulation of lipocalin-2 alleviates depressive-like behaviors in mice through modulation of microglial activation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Integrated approaches to geriatric mental disorders: pathophysiology, interventions, and precision medicine horizons.Frontiers in psychiatry · 2026Review
- Mitochondrial CISD1 Modulates Microglial Metabolic Reprogramming to Drive Stress Susceptibility in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual roles of lactate and lactylation modification in the nervous system: neuroprotection and neuroinjury.Frontiers in aging neuroscience · 2026Review
- Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise.Journal of neurochemistry · 2025Review
- Inflammation in Obstructive Sleep Apnea: A Global Bibliometric Perspective.Nature and science of sleep · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Depression has been widely recognized as an important accelerating factor contributing to the aggravation of cognitive decline in Alzheimer's disease (AD) patients. Previous studies show that microglia-mediated neuroinflammation is a common and critical event in the etiology of both depression and dementia, but whether and how microglia participate in the process of depression-exacerbating AD pathology is largely unknown. By establishing the learned helplessness depression model on 5×FAD mice, we confirmed that depression can indeed promote Aβ plaque deposition and deteriorate the cognitive performance of the AD mice. Importantly, we found that microglial lactate concentration is dramatically increased in the depressed AD brain, leading to activation of potassium channel Kv1.3 likely through non-direct-lactylation. The activated Kv1.3 further facilitates Aβ-containing exosome spreading from microglia in the vicinity of Aβ plaque into the surrounding brain tissue. Notably, conditional knock-out of Kv1.3 in microglia can reverse the depression-induced acceleration of AD pathology and cognitive decline. Together, our study highlights an important function of microglia Kv1.3 in the promotion of Aβ propagation in the context of depression-exacerbating AD pathology.
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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.