Investigati̇on of TLR4/NF-KB/GSK-3β signaling pathway in behavior changes caused by EARLY social isolation in rats

Havva Nur Özçetin, Investigation of TLR4/NF-κB/GSK-3β Signaling Pathway in Behavior Changes Caused by Early Social Isolation in Rats, Zonguldak Bülent Ecevit University, Health Sciences Institute, Department of Physiology, Master Thesis, Zonguldak, 2021. Social isolation is the lack of social interaction with other creatures. Social isolation in animals living with social groups, such as rodents, shows similar results to behavioral changes observed in humans. Neuropsychiatric disorders begin in the early stages of life, and exposure to a stress factor such as social isolation during this period negatively affects brain development. Our aim in this study is to examine the TLR4/NF-κB/GSK-3β signaling pathway in behavioral changes caused by early social isolation. In the literature, it has been shown that there is an increase in the expression of innate immune proteins such as Toll-like receptors in patients with depression. Toll-like receptor 4 is the first line of defense in the brain and is a key regulator of adaptive immune responses. TLR4 triggers microglial activation via Nuclear Factor kappa B, which plays a role in another innate immune response. Glycogen synthase kinase-3β is a regulator of the TLR signaling pathway and can induce NF-κB activity. GSK-3β activity is also associated with increased oxidative stress. In our study, 18 male Wistar Albino rats were used. Rats were divided into control and experimental groups. While the rats in the control group were housed under normal conditions, the rats in the experimental group were kept in isolation in individual cages for 6 weeks. Depression-like behavior was evaluated with the forced swimming test, and anxiety-like behavior was evaluated with the open field test. TLR4, NF-κB, GSK-3β levels were measured by ELISA method. The levels of malondialdehyde, which is a marker of oxidative stress, and reduced glutathione, an antioxidant, were measured in the prefrontal cortex. Statistical significance between groups was determined by the Mann-Whitney U test. At the end of behavioral tests, it was observed that anxiety and depression-like behaviors increased in rats exposed to social isolation. As a result, it has been found that social isolation can trigger depression-like behavior by causing neuroinflammation and increased oxidative stress. Key Words: GSK-3β, NF-κB, Oxidative stress, Social isolation, TLR4