Reducing post-traumatic anxiety by immunization.
Trafficking of T lymphocytes to specific organs, such as the skin and lungs, is part of the body's defense mechanism following acute psychological stress. Here we demonstrate that T lymphocytes are also trafficking to the brain in response to psychological stress and are needed to alleviate its negative behavioral consequences. We show that short exposure of mice to a stressor (predator odor) enhanced T-cell infiltration to the brain, especially to the choroid plexus, and that this infiltration was associated with increased ICAM-1 expression by choroid plexus cells. Systemic administration of corticosterone could mimic the effects of psychological stress on ICAM-1 expression. Furthermore, we found that the ability to cope with this stress is interrelated with T-cell trafficking and with the brain and hippocampal BDNF levels. Immunization with a CNS-related peptide reduced the stress-induced anxiety and the acoustic startle response, and restored levels of BDNF, shown to be important for stress resilience. These results identified T cells as novel players in coping with psychological stress, and offers immunization with a myelin-related peptide as a new therapeutic approach to alleviate chronic consequences of acute psychological trauma, such as those found in posttraumatic stress disorder.
Lewitus
Gil M
GM
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Cohen
Hagit
H
Ministry of Health, Mental Health Center Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Schwartz
Michal
M
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: michal.schwartz@weizmann.ac.il.
D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000150:complications*; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D022223:Vaccines, Subunit; D018799:Intercellular Adhesion Molecule-1; D003345:Corticosterone