ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
A novel role for brain interleukin-6: facilitation of cognitive flexibility in rat orbitofrontal cortex.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
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- Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.BMC neuroscience · 2023Review
- Low-dose lithium adjunct to atypical antipsychotic treatment nearly improved cognitive impairment, deteriorated the gray-matter volume, and decreased the interleukin-6 level in drug-naive patients with first schizophrenia symptoms: a follow-up pilot study.Schizophrenia (Heidelberg, Germany) · 2023Article
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- Roles of non-receptor tyrosine kinases in pathogenesis and treatment of depression.Journal of integrative neuroscience · 2022Review
- Neuroinflammatory Signaling in the Pathogenesis of Alzheimer's Disease.Current neuropharmacology · 2022Review
- Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk.Translational psychiatry · 2021Article
- Adulthood systemic inflammation accelerates the trajectory of age-related cognitive decline.Aging · 2021Article
- Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders.Frontiers in neuroscience · 2021Review
- Beneficial Effect of Immune-Enhanced Enteral Nutrition on Immune Function in Patients With Severe Neurological Diseases: A Single-Center Randomized Controlled Trial.Frontiers in nutrition · 2021Article
- Optogenetically-induced long term depression in the rat orbitofrontal cortex ameliorates stress-induced reversal learning impairment.Neurobiology of stress · 2020Article
- Gamma Visual Stimulation Induces a Neuroimmune Signaling Profile Distinct from Acute Neuroinflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Ciliary neurotrophic factor signaling in the rat orbitofrontal cortex ameliorates stress-induced deficits in reversal learning.Neuropharmacology · 2019Article
- The influence of central interleukin-6 on behavioral changes associated with acute alcohol intoxication in adult male rats.Alcohol (Fayetteville, N.Y.) · 2019Article
- Assessment of Extracellular Cytokines in the Hippocampus of the Awake Behaving Rat Using Large-Molecule Microdialysis Combined with Multiplex Arrays After Acute and Chronic Ethanol Exposure.Alcoholism, clinical and experimental research · 2019Article
- Understanding the Relation Between Early-Life Adversity and Depression Symptoms: The Moderating Role of Sex and an Interleukin-1β Gene Variant.Frontiers in psychiatry · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cytokines, small proteins released by the immune system to combat infection, are typically studied under inflammatory conditions. However, these molecules are also expressed in the brain in basal, nonpathological states, where they can regulate neuronal processes, such as learning and memory. However, little is known about how cytokine signaling in the brain may influence higher-order cognitive functions. Cognitive flexibility is one such executive process, mediated by the prefrontal cortex, which requires an adaptive modification of learned behaviors in response to environmental change. We explored the role of basal IL-6 signaling in the orbitofrontal cortex (OFC) in reversal learning, a form of cognitive flexibility that can be measured in the rat using the attentional set-shifting test. We found that inhibiting IL-6 or its downstream JAK/STAT signaling pathway in the OFC impaired reversal learning, suggesting that basal IL-6 and JAK/STAT signaling facilitate cognitive flexibility. Further, we demonstrated that elevating IL-6 in the OFC by adeno-associated virus-mediated gene delivery reversed a cognitive deficit induced by chronic stress, thus identifying IL-6 and the downstream JAK/STAT signaling pathway as potentially novel therapeutic targets for the treatment of stress-related psychiatric diseases associated with cognitive dysfunction.
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Registered trials
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.