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Objectives: One of the main adult neurogenesis regions is located in subgranular layer dentate gyrus of hippocampus. New neurons which are created here are integrated into the hippocampal network. The exact function of adult neurogenesis in hippocampus is yet unknown, although it was proved to play a role in some forms of hippocampal learning and memory. Ablation of neurogenesis provides a powerful tool to look into the function of neurogenesis in adult brain. Cytostatic temozolomide has negative effects on quickly dividing cells in all organism, therefore is important to determine minimal dose, which would successfully block formation of new neurons.
Methods: This project aims at determining the optimum dose of temozolomide in laboratory Long-Evans rat, which effectively blocks proliferation of new cells but has minimal side-effects of the treatment. Fifty mg/kg dose, which has been previously used in mouse, had destructive effects to organism of laboratory rat. Temozolomide was administered intra-gastrically for four weeks, three times in week. We had four groups with different doses: 10.25 and 40 mg/kg. Neurogenesis was detected by BrdU staining and şuorescence. During the experiment, blood tests with cell counting and control motor tests were conducted at several time points to determine the health of animals and assess the degree of recovery.
Results: The results of this dose-response study suggest that a dose of 25 mg/kg was optimal for Long-Evans rats, since it successfully ablates neurogenesis while causing minimal negative symptoms (despite the blood cell recovery was not complete), which were observed in 40 mg/kg dose.
Conclusion: We conclude that optimum dose for blocking adult neurogenesis and recovery of somatic function was found in 25 mg/kg
Acknowledgement: This research was supported by AV CR project M200111204 and by GACR 14-03627S.