Editors' ChoiceNeuroimmunology

Dazed and confused from infection

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Sci. Signal.  20 Jun 2017:
Vol. 10, Issue 484, eaao1213
DOI: 10.1126/scisignal.aao1213

TNF-α produced by circulating CX3CR1high monocytes causes the problems that infected individuals have with learning and remembering.

Infected individuals often experience temporary changes in behavior and have trouble learning and remembering. Learning and memory are associated with increased formation and density of dendritic spines. Garré et al. found that treatment with polyinosinic:polycytidylic [poly(I:C)], a mimic of viral double-stranded RNA, impaired the ability of mice to learn how to run on a rotarod. Both basal and learning-dependent dendritic spine elimination were increased in the motor cortex of these mice. The effect of poly(I:C) on dendritic spine stability and learning required the chemokine receptor CX3CR1 on circulating monocytes, rather than microglia, another CX3CR1-positive immune cell type in the central nervous system (CNS). In response to poly(I:C) injection, CX3CR1high monocytes in the circulation produced tumor necrosis factor–α (TNF-α), which was associated with increased concentrations of this proinflammatory cytokine in the cortex. TNF-α was required for the effects of poly(I:C) on dendritic spine stability and learning. In the associated commentary, Priller and Böttcher note that the blood-brain-barrier generally restricts the passage of proinflammatory cytokines such as TNF-α into the CNS, necessitating future studies to determine how synaptic plasticity is affected by TNF-α produced by circulating monocytes.

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