Mechanisms for interferon-?-induced depression and neural stem cell dysfunction.

ABSTRACT: New neurons generated by the neural stem cells (NSCs) in the adult hippocampus play an important role in emotional regulation and respond to the action of antidepressants. Depression is a common and serious side effect of interferon-? (IFN-?), which limits its use as an antiviral and antitumor drug. However, the mechanism(s) underlying IFN-induced depression are largely unknown. Using a comprehensive battery of behavioral tests, we found that mice subjected to IFN-? treatment exhibited a depression-like phenotype. IFN-? directly suppressed NSC proliferation, resulting in the reduced generation of new neurons. Brain-specific mouse knockout of the IFN-? receptor prevented IFN-?-induced depressive behavioral phenotypes and the inhibition of neurogenesis, suggesting that IFN-? suppresses hippocampal neurogenesis and induces depression via its receptor in the brain. These findings provide insight for understanding the neuropathology underlying IFN-?-induced depression and for developing new strategies for the prevention and treatment of IFN-?-induced depressive effects.

SUBMITTER: Zheng LS 

PROVIDER: S-EPMC4110771 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature