Prefrontal Kortekste NUDT6 İfadesindeki Değişikliklerin Sıçanda Depresyon-Benzeri ve Anksiyete-Benzeri Davranışa Etkileri

Abstract

Hökelekli, F.Ö. The Effects of NUDT6 Expression Changes in Prefrontal Cortex on Depression- and Anxiety-like Behaviour in Rats, Hacettepe University, Graduate School of Health Sciences PhD thesis in Basic Neurological Sciences (Neuroscience), Ankara, 2018. Natural antisense transcripts are mRNA molecules, which are synthesized from the anti-sense strand of a protein coding gene. They are complementary to the sense transcript and thought to regulate its expression. NUDT6 is the natural antisense transcript of FGF2 and is involved in the control of FGF2 expression. The antidepressant and anxiolytic effects of FGF2 makes it worth to study the role of NUDT6 in affective behaviour. Previously in our lab, chronic restraint stress was shown to decrease NUDT6 expression in prefrontal cortex (PFC). Based on this finding, we investigated the effects of NUDT6 expression changes in rat PFC on depression- and anxiety-like behaviors. NUDT6 was overexpressed and NUDT6 expression was knocked down by AAV2 injections. Depression-like behaviour was tested using sucrose preference test and forced swim test, anxiety-like behaviour was evaluated by elevated plus maze and light-dark box test and learning was investigated using passive avoidance test. The animals were sacrificed for molecular investigations. It was shown that NUDT6 overexpression in PFC is depressogenic and anxiogenic. NUDT6 knockdown in PFC, on the other hand, does not cause any significant changes on behavior. Additionally, it was shown that NUDT6 overexpression in PFC might have an influence on impulsivity-like behaviour, which needs to be addressed in future studies. It is of great importance to elicit the molecular mechanisms underlying NUDT6 effects in order to understand the pathogenesis of major depression and anxiety disorders.

Key Words: NUDT6, FGF2, antisense, depression, anxiety This study was supported by Hacettepe University Research Projects Coordination Unit with the project number THD-2016-11687.