Radiation Biology

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SU_39_2394 - The Impact of Tianeptine in the Prevention of Radiation-Induced Neurogenesis Inhibition

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

The Impact of Tianeptine in the Prevention of Radiation-Induced Neurogenesis Inhibition
T. Kutuk1, S. Akyurek2, D. Billur3, P. Bayram3, I. Dogan4, M. Bozkurt4, B. Can3, and S. C. Gokce2; 1Malatya Education and Research Hospital Department of Radiation Oncology, Malatya, Turkey, 2Ankara University School of Medicine Department of Radiation Oncology, Ankara, Turkey, 3Ankara University School of Medicine Department of Histology and Embryology, Ankara, Turkey, 4Ankara University School of Medicine Department of Neurosurgery, Ankara, Turkey

Purpose/Objective(s): Cranial radiotherapy (RT) is a frequently used treatment option, but its neurocognitive side effects emerge as a serious problem. Radiation inhibits hippocampal neurogenesis by induction of apoptosis and by decreasing the proliferation in the hippocampus. Tianeptine is an antidepressant drug and has been shown to induce hippocampal neurogenesis by reducing apoptosis and by providing a protective effect on proinflammatory cytokines. We aimed to demonstrate the effect of tianeptine on the inhibition of hippocampal neurogenesis and the apoptosis due to RT.

Materials/Methods: Fifty six Wistar Albino rats were divided into 4 groups consisting of a control (n = 14), tianeptine (n = 14), RT (n = 14) and tianeptine + RT (n = 14) groups. Tianeptine and RT+tianeptine groups were administered tianeptine by oral gavage 3 weeks before the first sacrification and until day 120. Groups consisting of RT protocols received 10 Gy cranial RT. Hippocampal samples from the rats in each group were collected at 5th hour (early effects) and 120th day (late effects) after the RT. Morphological and immunohistochemical examinations were performed to detect cell proliferation with Ki67, apoptosis with TUNEL and immature neurons with doublecortin (DCX) selective antibody.

Results: At 5th-hour post-RT, there was no statistically significant difference between the RT+tianeptine and the RT groups in terms of Ki-67(+) cell counts (p = 0.246). Ki67(+) cell count in the RT group was reduced compared with the control group (p<0.001). The difference in the number of DCX(+) cells between RT and RT+tianeptine groups was not statistically significant (p = 0.39). In the RT group, however, the number of DCX(+) cells was lower than the control group (p <0.001). In the RT group, more TUNEL (+) cells were observed than RT+tianeptine and the other groups, and the difference was statistically significant (p <0.001). There was no statistically significant difference between groups in terms of Ki67(+) cell counts at 120 days post-RT (p = 0.1). The number of DCX (+) cells in the RT group was lower than the control group (p <0.001), but there was no statistically significant difference in the number of DCX (+) cells between RT and RT+tianeptine groups (p = 1). In the RT group, more TUNEL (+) cells were observed than RT+tianeptine and the other groups, and it was statistically significant (p <0.001).

Conclusion: To the best of our knowledge, this is the first study in the literature examines the effect of tianeptine on neurogenesis induction observed in hippocampus due to RT. Our study showed that there is an increase in hippocampal apoptosis and a decrease in neurogenesis due to RT. Tianeptine reduced RT-induced apoptosis but did not have a statistically significant effect on neurogenesis. However, we believe that the effect of tianeptine on neurogenesis may be more pronounced in lower doses of cranial RT because of the fact that it has relieved inhibition of neurogenesis following 10 Gy cranial RT.

Author Disclosure: T. Kutuk: None. S. Akyurek: None. D. Billur: None. B. Can: None.

Tugce Kutuk, MD

Biography:
Tugce Kutuk is a radiation oncologist at the Malatya Education and Research Hospital in Turkey. She was born in 1988 in Adana, Turkey. She graduated from Adana Science High School in 2005 and Hacettepe University School of Medicine in 2011. She completed the scientific part of her residency in radiation oncology at Ankara University in 2018 and is continuing her obligatory service now.
She has been involved in an International Atomic Energy Agency project in radiotherapy planning of non-small cell lung cancer based on PET-CT since 2015. Her thesis is titled the Impact of tianeptine in the prevention of radiation-induced neurocognitive impairment and she gained the best presentation award with this research at the 13th National Radiation Oncology Congress in Turkey. Her research was presented in international and national scientific congresses before.
She speaks Turkish and English, and is a member of Turkish Association of Neurooncology and Turkish Association of Radiation Oncology.

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