Long-term intake of thermo-induced oxidized oil results in anxiety-like and depression-like behaviors: involvement of microglia and astrocytes.

Frequent consumption of fried foods has been strongly associated with a higher risk of anxiety and depression, particularly among young individuals. The existing evidence has indicated that acrylamide produced from starchy foods at high temperatures can induce anxious behavior. However, there is limited research on the nerve damage caused by thermo-induced oxidized oil (TIOO). In this study, we conducted behavioral tests on mice and found that prolonged consumption of TIOO led to significant anxiety behavior and a tendency toward depression. TIOO primarily induced these two emotional disorders by affecting the differentiation of microglia, the level of inflammatory factors, the activation of astrocytes, and glutamate circulation in brain tissue. By promoting the over-differentiation of microglia into M1 microglia, TIOO disrupted their differentiation balance, resulting in an up-regulation of inflammatory factors (IL-1β, IL-6, TNF-α, NOS2) in M1 microglia and a down-regulation of neuroprotective factors IL-4/IL-10 in M2 microglia, leading to nerve damage. Moreover, TIOO activated astrocytes, accelerating their proliferation and causing GFAP precipitation, which damaged astrocytes. Meanwhile, TIOO stimulates the secretion of the BDNF and reduces the level of the glutamate receptor GLT-1 in astrocytes, leading to a disorder in the glutamate-glutamine cycle, further exacerbating nerve damage. In conclusion, this study suggests that long-term intake of thermo-induced oxidized oil can trigger symptoms of anxiety and depression.