Investigation of behavioral effects of dexmedetomidine in the zebrafish amyloid beta toxicity model

Background: Dexmedetomidine is known to exhibit anti-inflammatory and neuroprotective properties and reduce the incidence of postoperative cognitive disorders. The aim of our study; to investigate the effect of low or high dose dexmedetomidine applications on neurobehavioral properties in amyloid beta toxicity model created in adult zebrafish and to observe whether dexmedetomidine has a neuroprotectant effect in this model. Materials and Methods: In the study, Aβ-induced Alzheimer's Disease model was created by injecting Aβ peptide into the brain of zebrafish by cerebroventricular injection. In the presence or absence of Aβ toxicity to adult zebrafish; low (250 µM) or high (500 µM) dose dexmedetomidine was administered by retro-orbital injection method. A total of 24 wild-type zebrafish, aged between 6-12 months, were used in 4 groups and 6 in each group. They were divided into groups as Group 1 (Sham group), Group 2 (Aß toxicity group), Group 3 (group exposed to 250 µM dexmedetomidine with Aβ toxicity), Group 4 (group exposed to 500 µM dexmedetomidine with Aß toxicity). Social interaction, mirror biting and Novel tank behavior tests were performed on zebrafish after Aβ and dexmedetomidine applications. Afterwards, dissection of the telencephalon was performed and Alzheimer's gene expression analyzes by qPCR and GFAP validation were performed by Western Blot. Results: In qPCR gene expression analyzes, a statistically significant decrease was observed in the results of psen1, psen2 and appa genes in the "Aβ-Low Dose Dex" and "Aβ-High Dose Dex" experimental groups when compared to the "Aβ-PBS" group. In addition, there was no significant difference between the "Aβ-Low-Dose Dex" and "Aβ-High-Dose Dex" groups. For the pcna gene, the increase in the "Aβ-Low Dose Dex" and "Aβ-High Dose Dex" experimental groups was statistically significant compared to the "PBS-PBS" group. According to Western blot analysis, a statistically significant increase was observed in the relative expression of GFAP in G2 compared to G1. A statistically significant decrease in xv GFAP expression was observed when dexmedetomidine administered G3 and G4 experimental groups were compared with G2. Conclusions: In line with the data obtained, it was determined that low (250 µM) and high (500 µM) doses of dexmedetomidine, an α2 adrenergic receptor agonist, had neuroprotective effects in the zebrafish amyloid beta toxicity model. No statistically significant results were obtained in behavioral tests. Keywords: Alzheimer's disease, dexmedetomidine, zebrafish, anesthesia, behavior, neuroprotective