title: Immune status influences fear and anxiety responses in mice after acute stress exposure.
abstract: Significant evidence suggests that exposure to traumatic and/or acute stress in both mice and humans results in compromised immune function that in turn may affect associated brain processes. Additionally, recent studies in mouse models of immune deficiency have suggested that adaptive immunity may play a role during traumatic stress exposure and that impairments in lymphocyte function may contribute to increased susceptibility to various psychogenic stressors. However, rodent studies on the relationship between maladaptive stress responses and lymphocyte deficiency have been complicated by the fact that genetic manipulations in these models may also result in changes in CNS function due to the expression of targeted genes in tissues other than lymphocytes, including the brain. To address these issues we utilized mice with a deletion of recombination-activating gene 2 (Rag2), which has no confirmed expression in the CNS; thus, its loss should result in the absence of mature lymphocytes without altering CNS function directly. Stress responsiveness of immune deficient Rag2(-/-) mice on a BALB/c background was evaluated in three different paradigms: predator odor exposure (POE), fear conditioning (FC) and learned helplessness (LH). These models are often used to study different aspects of stress responsiveness after the exposure to an acute stressor. In addition, immunoblot analysis was used to assess hippocampal BDNF expression under both stressed and non-stressed conditions. Subsequent to POE, Rag2(-/-) mice exhibited a reduced acoustic startle response compared to BALB/c mice; no significant differences in behavior were observed in either FC or LH. Furthermore, analysis of hippocampal BDNF indicated that Rag2(-/-) mice have elevated levels of the mature form of BDNF compared to BALB/c mice. Results from our studies suggest that the absence of mature lymphocytes is associated with increased resilience to stress exposure in the POE and does not affect behavioral responses in the FC and LH paradigms. These findings indicate that lymphocytes play a specific role in stress responsiveness dependent upon the type, nature and intensity of the stressor.
authors: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States.
authors: Sarah M
authors: SM
authors: Clark
authors: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors: Joseph
authors: J
authors: Sand
authors: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, United States.
authors: T Chase
authors: TC
authors: Francis
authors: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors: Anitha
authors: A
authors: Nagaraju
authors: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors: Kerry C
authors: KC
authors: Michael
authors: Center for Vascular and Inflammatory Diseases, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States.
authors: Achsah D
authors: AD
authors: Keegan
authors: Department of Psychology, Rutgers University, Newark, NJ, United States.
authors: Alexander
authors: A
authors: Kusnecov
authors: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States.
authors: Todd D
authors: TD
authors: Gould
authors: Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, United States; Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, United States. Electronic address: ltonelli@psych.umaryland.edu.
authors: Leonardo H
authors: LH
authors: Tonelli
mesh_terms: D000818:Animals; D001007:Anxiety / Q000276:immunology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003213:Conditioning, Psychological; D004268:DNA-Binding Proteins / Q000235:genetics; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009043:Motor Activity; D013216:Reflex, Startle; D013315:Stress, Psychological / Q000276:immunology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse
keywords: Acoustic startle; Anxiety; BDNF; Fear; Lymphocytes; Open field test; Stress; Western blots