ArticleTranslational psychiatry2015
A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors.
Article in Translational psychiatry, 2015. 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.
- Review
- TNF-dependent regulation of synaptic plasticity and neuronal activity: implications for psychiatric disorders.Molecular psychiatry · 2026Review
- Psycho-cardiovascular interaction network in cardiovascular health and disease: signaling pathways and molecular mechanisms.Precision clinical medicine · 2026Review
- SHANK3 Deficiency in AgRP Neurons Inhibits Diet-Induced Obesity by Activating p38α.Neuroscience bulletin · 2026Article
- Bidirectional crosstalk between microglia and serotonin signaling in neuroinflammation and CNS disorders.Frontiers in immunology · 2025Review
- Flavins and Flavoproteins in the Neuroimmune Landscape of Stress Sensitization and Major Depressive Disorder.Journal of inflammation research · 2025Review
- Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling.Journal of neuroinflammation · 2024Article
- Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons.Molecular autism · 2024Article
- Functional and pathological consequences of being fast on the uptake: Protein kinase G and p38α MAPK regulation of serotonin transporters.Current research in physiology · 2024Review
- Intestinal Predictors of Whole Blood Serotonin Levels in Children With or Without Autism.Journal of autism and developmental disorders · 2022Article
- Serotonin Transporter Ala276 Mouse: Novel Model to Assess the Neurochemical and Behavioral Impact of Thr276 Phosphorylation In Vivo.Neurochemical research · 2022Review
- Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse.Frontiers in cellular neuroscience · 2021Article
- Xinkeshu Improves Endothelial Function and Augments Reendothelialization Capacity in Coronary Artery Disease with Anxiety/Depression.Oxidative medicine and cellular longevity · 2021Article
- Is p38 MAPK Associated to Drugs of Abuse-Induced Abnormal Behaviors?International journal of molecular sciences · 2020Review
- Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects.Molecular psychiatry · 2020Article
- Functions of p38 MAP Kinases in the Central Nervous System.Frontiers in molecular neuroscience · 2020Review
- p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Neuronal MAP kinase p38α inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour.Scientific reports · 2018Article
- Bacterial Lipopolysaccharide Increases Serotonin Metabolism in Both Medial Prefrontal Cortex and Nucleus Accumbens in Male Wild Type Rats, but Not in Serotonin Transporter Knockout Rats.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Alterations in central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and peripheral immune activation have been linked to multiple neuropsychiatric disorders, including depression, schizophrenia and autism. The antidepressant-sensitive 5-HT transporter (SERT, SLC6A4), a critical determinant of synaptic 5-HT inactivation, can be regulated by pro-inflammatory cytokine signaling. Systemic innate immune system activation via intraperitoneal lipopolysaccharide (LPS) injection rapidly elevates brain SERT activity and 5-HT clearance. Moreover, the pro-inflammatory cytokine interleukin (IL)-1β rapidly stimulates SERT activity in raphe nerve terminal preparations ex vivo, effects that are attenuated by pharmacological p38 MAPK inhibition. To establish a role of serotonergic p38α MAPK signaling in LPS/IL-1β-induced SERT regulation and attendant behavioral responses, we pursued studies in mice that afford conditional elimination of p38α MAPK in 5-HT neurons (p38α(5HT-)). We found p38α(5HT-) and control (p38α(5HT+)) littermates to be indistinguishable in viability and growth and to express equivalent levels of SERT protein and synaptosomal 5-HT transport activity. Consistent with pharmacological studies, however, IL-1β fails to increase SERT activity in midbrain synaptosomes prepared from p38α(5HT-) animals. Moreover, although LPS elevated plasma corticosterone and central/peripheral pro-inflammatory cytokines in p38α(5HT-) animals, elevations in midbrain SERT activity were absent nor were changes in depressive and anxiety-like behaviors observed. Our studies support an obligate role of p38α MAPK signaling in 5-HT neurons for the translation of immune activation to SERT regulation and 5-HT-modulated behaviors.
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