Vaccine for the mind: Immunity against self at the choroid plexus for erasing biochemical consequences of stressful episodes

Stressful episodes or chronic stress can shape our brain, leaving behind their biochemical signature on the neural tissue parenchyma. Mitigating such detrimental effects on the central nervous system (CNS) would be advantageous for coping with stress. While the underlying mechanisms that facilitate this response are still a mystery, recent studies demonstrate that boosting specific components of circulating immunity can potentially enhance our ability to deal with stressors. Yet, the fact that the adaptive arm of the immune system is largely excluded from directly interacting with the healthy CNS raises a key question as to how these cells exert their beneficial effects. Boosting immunity against self by active immunization with CNS-derived peptides was shown to reduce anxiety levels and to modulate hippocampal plasticity. These effects correlate with increased immune surveillance at the borders of the brain; specifically, at the choroid plexus (CP), an epithelial layer that resides at the junction between the blood circulation, and the brain and plays a key role in maintaining and restoring brain homeostasis, regulating cerebrospinal-fluid (CSF) production and neurotropic factors composition. Here, we suggest that immunomodulation of this site by active immunization could protect against stressful episodes, thereby providing a therapeutic, as well as preventive, vaccine for the mind against stress and depression.