Further evidence for the role of interferon-gamma on anxiety- and depressive-like behaviors: Involvement of hippocampal neurogenesis and NGF production

A series of evidence suggests that interferon-gamma (IFN-γ) plays an important role in central nervous system (CNS) functions. However, previous studies have obtained inconsistent results regarding the role of IFN-γ in modulating emotion-related behaviors. The present study aimed to evaluate the behavioral profile of IFN-γ knockout (K.O.) mice in models of anxiety and depression. Male C57Bl6 wild type (WT) or IFN-γ K.O. mice were submitted to the following tests: contextual fear conditioning (CFC), elevated plus maze (EPM), open field (OF) and forced swimming test (FST). To explore the possible neurobiological mechanisms involved, we also assessed hippocampal neurogenesis by means of hippocampal doublecortin expression, and the levels of brain-derived neurothophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus and prefrontal cortex. Our results suggested that IFN-γ K.O. mice exhibited an anxiogenic profile in CFC, EPM and OF tests. In FST, the K.O. group spent more time immobile than the WT group. The number of doublecortin positive cells was reduced in the dentate gyrus, and the expression of NGF was down regulated in the prefrontal cortex of IFN-γ K.O. mice. Our results suggest that IFN-γ is involved in CNS plasticity, contributing to the modulation of anxiety and depressive states.