ArticleNeuroscience bulletin2021
Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice.
Article in Neuroscience bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Life Cycle and Circadian Rhythms in Central Resident Immunity and Neuropsychiatric Pathology.Neuroscience bulletin · 2026Review
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Dynamic glycosylation remodeling in neurological disorders.Frontiers in molecular neuroscience · 2025Review
- Functional Changes in Astrocytes Lead to Cognitive Deficits After Social Deprivation.Neuroscience bulletin · 2024Article
- Now We Can Tame the Wild West of Controlling Astrocytes for Treating Neocortical Epilepsy.Neuroscience bulletin · 2023Article
- A Review of Research on the Association between Neuron-Astrocyte Signaling Processes and Depressive Symptoms.International journal of molecular sciences · 2023Review
- O-GlcNAc transferase in astrocytes modulates depression-related stress susceptibility through glutamatergic synaptic transmission.The Journal of clinical investigation · 2023Article
- Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice.Nature communications · 2023Article
- Astrocyte regulation of synaptic signaling in psychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment.Handbook of experimental pharmacology · 2023Review
- Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning.Molecular neurobiology · 2022Article
- Association of Increased Amygdala Activity with Stress-Induced Anxiety but not Social Avoidance Behavior in Mice.Neuroscience bulletin · 2022Article
- Astrocytes in depression and Alzheimer's disease.Frontiers of medicine · 2021Review
- Mitochondrial Events Determine the Status of Hippocampal Cells in the Post-Ischemic Period.Neuroscience bulletin · 2021Article
- Article
- Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice.Nature communications · 2021Article
- Elevated L-lactate Promotes Major Cellular Pathologies Associated with Neurodegenerative Diseases.Neuroscience bulletin · 2021Article
- Proteomic Profiling of Astrocytic O-GlcNAc Transferase-Related Proteins in the Medial Prefrontal Cortex.Frontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless. Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex (mPFC) when mice experienced the forced swimming test (FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4 (MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocyte-derived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.
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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.