The role of cytokines in modulating learning and memory and brain plasticity

Abstract

Cytokines are proteins secreted in the central nervous system by neurons, microglia, astrocytes and infiltrating peripheral immune cells under physiological and pathological conditions. Over the last 20 years, a growing number of reports have investigated the effects of these molecules on brain plasticity. In this review, we describe how the key cytokines interleukin 1β, interleukin 6 and tumour necrosis factor α were found to support long-term plasticity and learning and memory processes in physiological conditions. In contrast, during inflammation where cytokines levels are elevated such as in models of brain injury or infection, depression or neurodegeneration, the effects of cytokines are mostly detrimental to memory mechanisms, associated behaviours and homeostatic plasticity.

Keywords: Cytokines; IL-1β; IL-6; TNF-α; inflammation; plasticity.

Figure 1.

Summary of the effects of cytokines on learning, memory and plasticity.

Figure 2.

Overview of the major mechanisms of action of cytokines on plasticity and learning and memory. Stimuli of different intensity and duration activate the production of cytokines IL-1β, TNF-α and IL-6 that in turn modulate several metabolic and molecular pathways, ultimately affecting neurocircuits that regulate learning and memory function. The strength and duration of the stimulus determine the concentration and production levels of cytokines, leading the cytokine response to generate either beneficial effects on learning and memory or detrimental effects that ultimately progress towards neuronal death and cognitive deficits. Cytokine production also activates other inflammatory systems like PGE2, nitric oxide and other chemokines that will impact on the inflammatory status of the brain and the learning, memory and plasticity responses.