The Sirtuin 2 Inhibitor AK-7 Leads to an Antidepressant-Like Effect in Mice via Upregulation of CREB1, BDNF, and NTRK2 Pathways

Guclu E., Inan S. Y., Vural H. C.

Molecular Neurobiology, vol.59, no.11, pp.7036-7044, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 59 Issue: 11
  • Publication Date: 2022
  • Doi Number: 10.1007/s12035-022-03026-8
  • Journal Name: Molecular Neurobiology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.7036-7044
  • Keywords: AK-7, SIRT2, Neuroplasticity, Depression, Mice
  • Yozgat Bozok University Affiliated: No


Depression is one of the most important and serious health problems in developing countries which affects millions of people. It is associated with the decrease of the quality of life as well as suicides and mortality. The disease may show recurrent episodes in some patients. Obviously, not all the patients with depression could be treated properly, because some individuals are drug-resistant and the options for the therapy are limited. Therefore, it is crucial to investigate new molecules and pathways that may have possible antidepressant activity. Sirtuin (SIRT), known as a class III histone deacetylase, which is regulated by nicotinamide adenine dinucleotide (NAD +), is one of these molecules. In the current study, we investigated the possible antidepressant-like effect of SIRT2 inhibitor AK-7. For this purpose, behavioral tests were performed in chronic AK-7-treated mice, and the expression levels of BDNF, NGF, NTF3, CREB, NTRK2, ERK1, ERK2, and GAP43 genes were evaluated by qRT-PCR analysis in brain tissues. Protein levels for BDNF, CREB1, and NTRK2 were determined by western blot. Our data showed that AK-7 significantly decreased immobility time and showed antidepressant-like effect. In addition, AK-7 treatment significantly increased mRNA levels of CREB and NTRK2 and protein levels of CREB1, BDNF, and NTRK2. Finally, our results suggest that SIRT2 and AK-7 may have a potential role in the cellular mechanisms of depression.