Abstract
Lipopolysaccharides are pro-inflammation mediators that can induce inflammation in the serum, hippocampus, and cortex of animals. And lipopolysaccharide-induced neuroinflammatory state resulted in significant depression-like behaviors, including reduced locomotor activity in the open field test, reduced saccharin preference, added immobility time in tail suspension test and forced swimming test, decreased comb time in the splash test, and increased latency to food in the novelty suppressed feeding test time, and reduced the levels of neurotrophic factors and synaptic proteins, and decreased Nissl bodies. Treatment with Xiaoyao Pills ameliorated the depression-like behavior, decreased the levels of inflammatory indicators, increased those of neurotrophic factors and synaptic proteins, and restored Nissl bodies. Our study suggests that lipopolysaccharides induce inflammation and nerve injury, thereby leading to depression. Xiaoyao Pills could be considered a potential therapeutic candidate for inflammation-induced depression.
Highlights
Depression is one of the most common mental illnesses
Xiaoyao Pills Prevent LPS-Induced Depressive Behavior After intraperitoneal injection of LPS, the immobility time of the mice was prolonged in the TST and forced swimming test (FST) compared with the control group (P < 0.05), indicating that LPS treatment induced depression-related behavior
We found that the transcription levels of interleukin 6 (IL-6) and Tumor necrosis factor alpha (TNF-α) were upregulated in the cortex and hippocampus following LPS administration, whereas, rats administered with Xiaoyao Pills (XYW) (1.86 g·kg-1) for 2 weeks by gavage, displayed a lower expression of IL-6 and TNF-α in the cortex and hippocampus than the model group (P < 0.05)
Summary
Depression is one of the most common mental illnesses. It has many pathogenic factors, which are related to gene and environment. Secretion of more proinflammatory cytokines [such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)] are reported in both patients with depression and animal models of depression (Gold, 2015). These cytokines affect neurotransmission and plasticity in the brain and suppress neurogenesis. Bacterial endotoxin lipopolysaccharide (LPS) challenge stimulates the acute inflammatory response and leads to depressive symptoms in humans and Abbreviations: XYW, Xiaoyao Pills; FLX, Fluoxetine hydrochloride; AMT, Amitriptyline; LPS, Lipopolysaccharide; IL-6, Interleukin 6; TNF-α, Tumor necrosis factor alpha; IDO, Indoleamine 2,3-dioxygenase; 5-HT, 5-hydroxytryptamine; BDNF, Brain-derived neurotrophic factor; NGF, Nerve growth factor; TrkB, Tropomyosin receptor kinase B; TrkA, Tropomyosin receptor kinase A; CREB, cAMP response element-binding protein; PSD95, postsynaptic density protein 95; SYP, synaptophysin; BrdU, 5-Bromo-2-deoxyUridine; NeuN, Vertebrate neuron-specific nuclear protein; OFT, open field test; TST, tail suspension test; FST, forced swimming test; ST, splash test; NSFT, novelty suppressed feeding test; SPT, sucrose preference test
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