Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus

To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57B1/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 mu g/mu l methylated BSA) or staphylococcus enterotoxin B (EC50 of 0.25 mu g/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC50 of 0.5 mu g/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low ( 0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.-Wolf, S. A., Steiner, B., Wengner, A., Lipp, M., Kammertoens, T., Kempermann, G. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus. FASEB J. 23, 3121-3128 (2009). www.fasebj.org