Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences

• Published in: Neurobiology of learning and memory 2014-11, Vol.115, p.68-77
• Main Authors: Donzis, Elissa J., Tronson, Natalie C.
• Format: Article
• Language: English
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Cognition & reasoning; Cytokine; Cytokines; Cytokines - physiology; Epigenetic modification; Fundamental and applied biological sciences. Psychology; Humans; Interleukin-1beta - physiology; Interleukin-6 - physiology; Learning; Learning - physiology; Memory; Memory - physiology; Memory Modulation; Neurobiology; Neurogenesis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Signal transduction; Signal Transduction - physiology; Tumor Necrosis Factor-alpha - physiology
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2014.08.008

•Inflammatory signaling modulates learning, memory and synaptic plasticity.•Networked interactions of cytokines are crucial to understanding effects on memory.•Intracellular signaling integrates the effects of opposing cytokines.•Epigenetic modifications and neurogenesis may mediate persistent changes in memory. This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition.