Effect of intermittent fasting on semaphorins in an In Vivo experimental Alzheimer model

EFFECT OF INTERMITTENT FASTING ON SEMAPHORINS IN AN IN VIVO EXPERIMENTAL ALZHEIMER MODEL- In addition to pharmacological and other treatments, the beneficial effects of intermittent fasting (IF) are also known in Alzheimer's disease (AD), a neurodegenerative disease with an increasing prevalence and socioeconomic burden in society (Nicolas & Nolan, 2022). Mechanisms such as neuronal stability, neuroplasticity and neurogenesis play important roles in this effect of IF, which is a nutritional pattern applied in the form of free eating between fasting periods (Elias et al., 2023). Semaphorins, one of the main components of perineural interactions, are a family of extracellular signaling molecules that mediate cell-cell communication and have important roles in the pathophysiology of AD (Quintremil et al., 2019). However, the effect of semaphorins on IF-induced changes in AD is unknown. The main purpose of our study is to investigate the effect of semaphorins on AD pathogenesis/AD treatment. In addition, it is aimed to guide the application of intermittent fasting in clinical and daily practice as a cost-effective treatment method and thus contribute to reducing the serious socioeconomic burden caused by AD in the long term. In our study, rats were divided into 4 groups (n = 8); Control, IF, Model AD and Model AD+IF. To establish the AD model (AHM), animals were administered AlCl3 (50 mg/kg-po [in drinking water]) for 20 weeks and D galactose (60 mg/kg/day-i.p) for 10 weeks. Then, in order to verify the model, behavioral tests (Morris Water Maze, Open field test) and serum t-tau level measurement were performed on the animals. For IF application, feeding of animals was restricted to 8 hours (09.00–17.00/ad libitum) for 3 months after the 20th week. At the end of the experiment, behavioral and ELISA tests were repeated and Sema-3A, Sema-4C, Sema-7A, Nrp1, Nrp2, AchE and p-Tau levels were determined in the animal brain tissues by indirect immunohistochemistry method. In our study, in addition to behavioral and biochemical parameters in the AD model, AD-related molecules such as p-Tau, AchE, Sema 3A, Nrp 1 were detected at higher levels than the control, and these effects were mostly reversed with IF treatment. Sema 4C and Nrp 2 levels decreased in AD models, but the effect of intermittent fasting on these was found to be low. One of the most important results of the study, the low levels of Sema 7A related to the immune system in the IF group, reveals the importance of neuroinflammatory/neuroimmune pathways in the treatment of AD. Key words: Alzheimer's Disease, intermittent fasting, semaphorin, tau, neuropilin,