Neuroimmune consequences of and contributions to affective mood states
Chronic psychosocial stress in animals alters the activation status of the brain’s immune cells—the microglia — and affects the status of immune cells in the periphery. Neuronal stress circuits engage a bi-directional dialog between the brain and central and peripheral immune systems involving anatomical, humoral, and cellular mechanisms. The neuroimmune communication pathways serve to achieve internal homeostasis. Disequilibrium in the system, if sustained or severe, results in disease. We are studying neuroimmune relationships in chronic stress paradigms to understand how they play out to affect behavior and CNS structure and function. The immune system is divided into an innate arm mediating rapid general immunity and an adaptive arm mediating delayed acquired cellular immunity. We are studying both arms. Stress-activated microglia are studied in a number of in vivo and ex vivo assays. The picture shows an assay for reactive oxygen species (ROS) in microglia and other cells in the chronic stress model.
Our studies of the effect of peripheral immune cells on behavior and stress circuits have focused on the model of adoptive transfer of lymphocytes into mice that lack mature lymphocytes. Cells taken from stressed but not unstressed mice confer an antidepressant effect on the host mice after repopulating the immune organs of the host mouse, as shown in the photograph of the labeled T cells (red) in meninges covering the brain of the host mouse. Studies are underway to understand the mechanisms for this novel effect.
- Lehmann M.L., Weigel T.K., Poffenberger C., Herkenham, M. The behavioral sequelae of social defeat require microglia and are driven by oxidative stress in mice. J. Neurosci., 2019, 39: 5594-5605. Full Text/Abstract
- Lehmann, M.L., Weigel, T.K., Cooper, H.A., Elkahloun, A.G., Kigar, S.L., Herkenham M. Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.Scientific Reports, 2018, 8:11240. Full Text/Abstract
- Lehmann M.L., Weigel T.K., Elkahloun A.G., Herkenham M. Chronic social defeat reduces myelination in the mouse medial prefrontal cortex. Sci Reports, 7: 46548, 2017. Full Text/Abstract
- Lehmann, M.L., Cooper, H.A., Maric, D., Herkenham, M. Social defeat induces depressive-like states and microglial activation without involvement of peripheral macrophages. J. Neuroimmunol.,13: 224, 2016. Full Text/Abstract
- Herkenham, M. and Kigar, S. L., Contributions of the adaptive immune system to mood regulation: mechanisms and pathways of neuroimmune interactions. Prog Neuropsychopharmacol. Biol. Psychiatry, 79: 49-57, 2017. Full Text/Abstract
- Brachman, R.A., Lehmann, M.L., Maric, D., and Herkenham, M. Lymphocytes from chronically stressed mice confer antidepressant-like effects to naïve mice. J. Neurosci., 35: 1530-1538, 2015 Full Text/Abstract
- Listwak, S.J., Rathore, P., and Herkenham, M. Minimal NF-kB activity in neurons. Neuroscience, 250: 282-299, 2013. Full Text/Abstract