Intra-mPFC injection of sodium butyrate promotes BDNF expression and ameliorates extinction recall impairment in an experimental paradigm of post-traumatic stress disorder
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 25، Issue: 9
Publish Year: 1401
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:
JR_IJBMS-25-9_015
تاریخ نمایه سازی: 20 شهریور 1401
Abstract:
Objective(s): Therapeutic strategies that facilitate extinction are promising in the treatment of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has a crucial role in neural plasticity, a process needed for the retention of fear extinction. In this study, we investigated the effects of local administration of a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu), on BDNF transcription and behavioral markers of extinction in the single prolonged stress (SPS) model of PTSD. Materials and Methods: NaBu was infused into the infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) of male rats. The freezing response was recorded as the criterion to assess fear strength on the day of extinction as well as ۲۴ hr later in the retention test. Other behavioral tests were also measured to evaluate the anxiety level, locomotor activity, and working memory on the retention day. HDAC activity and BDNF mRNA expression were evaluated after the behavioral experiments. Results: NaBu facilitated the recall of fear extinction in SPS rats (P<۰.۰۰۰۱). SPS rats had higher HDAC activity (P<۰.۰۰۰۱) and lower BDNF expression (P<۰.۰۵) than non-SPS animals. Also, anxiety was higher in the SPS group (P<۰.۰۰۰۱), but locomotor activity (P=۰.۶۱) and working memory (P=۰.۳۶) were not different between SPS and Non-SPS groups.Conclusion: Our findings provide evidence that the mechanism of action of NaBu in the improvement of extinction recall is mediated, in part, by enhancing histone acetylation and reviving BDNF expression in IL.
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Authors
Ahmad Mohammadi-Farani
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
Sajad Fakhri
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Cyrus Jalili
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Zahra Samimi
Department of Immunology, School of medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
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