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.
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Gil M
GM
Lewitus
Ministry of Health, Mental Health Center Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Hagit
H
Cohen
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: michal.schwartz@weizmann.ac.il.
Michal
M
Schwartz
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