For example, intraperitoneally administration of indoxyl sulfate can cause its further accumulation in the prefrontal cortical tissues and cerebrospinal fluid, which leads to behavioral changes and neurodegeneration, including anxiety, depression, and cognitive impairment, accompanied by impaired neuronal cell survival and neural stem cell activity, as well as disturbed expression of serotonin, corticosterone, and brain-derived neurotrophic factor (BDNF) [164]. This evidence concerns the gene BDNF and major depressive disorder.