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 C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/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 (EC(50) of 0.5 microg/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.
Neuronal Stem Cells Research Group, Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.
Susanne A
SA
Wolf
Barbara
B
Steiner
Antje
A
Wengner
Martin
M
Lipp
Thomas
T
Kammertoens
Gerd
G
Kempermann
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005938:Glucocorticoids / Q000032:analysis; D006624:Hippocampus / Q000166:cytology*; D007109:Immunity; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000276:immunology; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology
D005938:Glucocorticoids