Intermittent hypoxia exacerbated depressive and anxiety-like behaviors in the bleomycin-induced pulmonary fibrosis mice

Depression and anxiety are prevalent in patients with idiopathic pulmonary fibrosis (IPF). Recent researchers reveal that intermittent hypoxia (IH) increases the severity of bleomycin (BLM)-induced lung injury. However, experimental studies dealing with anxiety- and depression-like behavior in animal models of BLM-induced pulmonary fibrosis in a combination of IH are lacking, hence, this study aimed to investigate that. In this study, 80 C57BL/6J male mice were intratracheally injected with BLM or normal saline at day0 and then exposed to IH (alternating cycles of FiO 2 21 % for 60 s and FiO 2 10 % for 30 s, 40 cycles/hour, 8 h/day) or intermittent air (IA) for 21 days. Behavioral tests, including open field test (OFT), sucrose preference test (SPT) and tail suspension test (TST), were detected from day22 to day26. This study found that pulmonary fibrosis developed and lung inflammation were activated in BLM-induced mice, which were potentiated by IH. Significant less time in center and less frequency of entries in the centre arena in OFT were observed in BLM treated mice, and IH exposure further decreased that. Marked decreased percent of sucrose preference in SPT, and significant increased immobility time of the TST were detected in BLM treated mice and IH widen the gaps. The expression of ionized calcium-binding adaptor molecule (Iba1) was activated in the hippocampus of BLM instillation mice and IH enlarged it. Moreover, a positive correlation between hippocampal microglia activation and inflammatory factors was observed. Our results demonstrated that IH exacerbated depressive and anxiety-like behaviors in the BLM-induced pulmonary fibrosis mice. The changes in pulmonary inflammation-hippocampal microglia activation may be a potential mechanism in this phenomenon, which can be researched in future.