ABSTRACT
Deficiencies in the adaptive immune system have been linked to anxiety-like behaviours and stress reactivity. Mice lacking T lymphocytes through knockout of the T cell receptor (TCR) ß and δ chains were compared to wild type C57Bl/6 mice. Central stress circuitry gene expression was assessed following repeated restraint stress. TCRß-/-δ-/- mice showed an increased baseline plasma corticosterone and exaggerated changes in stress-related gene expression after repeated restraint stress. Sexual dimorphic stress responses were observed in wild-type C57Bl/6 mice but not in TCRß-/-δ-/- mice. These data suggest that T cell-brain interactions influence sex-differences in CNS stress circuitry and stress reactivity.
Subject(s)
Adaptive Immunity/immunology , Neuroimmunomodulation/physiology , Psychological Distress , Sex Characteristics , T-Lymphocytes , Animals , Brain/metabolism , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Antigen, T-Cell/deficiency , Restraint, Physical , Transcriptome/immunologyABSTRACT
Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor ß and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRß-/-δ- mice. Specifically, female TCRß-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRß-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRß-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior.
Subject(s)
Behavior, Animal/physiology , Brain/metabolism , Genes, T-Cell Receptor alpha/genetics , Genes, T-Cell Receptor beta/genetics , Sex Characteristics , T-Lymphocytes/metabolism , Animals , Anxiety/genetics , Anxiety/metabolism , Anxiety/pathology , Brain/pathology , Female , Male , Mice , Mice, Knockout , Organ Size/genetics , T-Lymphocytes/pathologyABSTRACT
The importance of the classical immune molecule, class I major histocompatibility complex to central nervous system function is one of the most surprising discoveries related to neuroimmunology in the past decade. Mice lacking both ß-2microglobulin and transporter associated with antigen processing (ß2M-/-TAP-/-) showed differences in basal behavior. In response to saline injection, ß2M-/-TAP-/- mice showed a significant hypothalamic pituitary adrenal activation that was not observed in wild type mice, while lipopolysaccharide-induced cytokine expression in the hypothalamus was similar in ß2M-/-TAP-/- and wild type mice. Overall, these data show that class I MHC plays an important role in behavior and stress reactivity.
