Investigation of neurobehavioral effects of irisin hormone in thoracic spinal cord injury model

Increased pro-inflammatory cytokines and loss of strength, chronic pain, increased stress and anxiety, decreased quality of life, and disruption of social life, along with motor and sensory impairments seen after spinal cord injury (SCI), bring along psychological problems. Exercise, which is one of the supportive treatments after injury, contributes positively to the healing process. In this study, we aimed to investigate the effects of irisin, an exercise-induced hormone, on depression and anxiety-like behaviors in rats with spinal cord injury model. 2 month old male Spraque Dawley (SD) rats with an average weight of 200 ± 2.5 g were used in the study. The rats were divided into 4 groups as Control, Sham, SCI+Deionized, SCI+Irisin. Spinal cord injury was induced in SCI+Deionized, SCI+Irisin groups by clip compression method at thoracic 10 level. After the model was established in the animals, 100ng/kg dose of irisin and deionized water were administered intraperitoneally for 6 weeks. Sucrose preference test, forced swimming test and elevated plus maze test were performed to evaluate depression and anxiety-like behaviors in rats after injury. At the end of the study, the animals were decapitated, blood samples were taken and the levels of inflammatory molecules tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6), Corticosterone and brain derived neurotrophic factor (BDNF) in serum samples were analyzed by Enzyme-linked immunosorbent assay (ELISA) test. At the end of the experimental studies, depression and anxiety-like behaviors were observed in the model animals. In the sucrose preference test, it was observed that irisin increased sucrose consumption compared to the deionized group and brought it closer to the control. In the challenging swimming test, climbing and swimming times, which decreased after SCI, increased when irisin was applied. In the elevated plus maze test in which anxiety-like behaviors were evaluated, an increase in the time spent in the closed arm was observed in post-model measurements. However, when irisin was applied, there was a decrease in the time spent in the closed arm and an increase in the time spent in the open arm. According to ELISA results in serum samples, IL-6, corticosterone, TNF-α values increased in the sham and injury group compared to the control group. In the group in which the model was created and irisin was administered, a significant decrease in these parameters was observed. There was no statistically significant difference in BDNF levels between the groups. In conclusion, in this study, for the first time, the positive effects of chronic administration of irisin, which is known to be induced by exercise, on depression and anxiety-like behaviors after SCI were observed in relation to some biochemical parameters. Based on these results, it is thought that irisin hormone may mediate the beneficial effect of exercise therapy on the improvement of behavioral functions after SCI.