Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction


Saral S. , Topçu A. , Alkanat M., Mercantepe T. , Akyıldız K. , Yıldız L., ...More

BEHAVIOURAL BRAIN RESEARCH, vol.408, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 408
  • Publication Date: 2021
  • Doi Number: 10.1016/j.bbr.2021.113290
  • Title of Journal : BEHAVIOURAL BRAIN RESEARCH
  • Keywords: Apelin-13, Cisplatin, Hippocampus, BDNF, TNF-?, BRAIN

Abstract

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. The aim of this study was to investigate the role of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway and the potential inhibitory effects of apelin-13 in the mechanism of cisplatin-induced hippocampal damage and cognitive impairment. Apelin-13 was administered to adult sprague dawley male rats at a dose of 20 nmol/kg every day for 4 weeks, cisplatin was administered at a dose of 5 mg/kg once a week for 4 weeks. The spatial and recognition memory tests of the rats were performed on the 5th week. BDNF and the inflammatory cytokines tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) levels were measured by ELISA in hippocampal homogenates. Pyramidal neuron and glial cell damage in the hippocampal CA1, CA3 and dentate gyrus (DG) were analyzed histologically. TrkB activity in the hippocampus was determined by immunohistochemical methods. Cisplatin impaired spatial and recognition memory in rats, while apelin-13 improved spatial memory but did not affect recognition memory. Cisplatin suppressed BDNF in the hippocampus while increased IL-1? and TNF-?. In contrast, apelin-13 administration increased BDNF but significantly suppressed TNF-? and IL-1B. Cisplatin caused pyramidal neuron and glial cell damage in CA1, CA3 and DG. In the cisplatin + apelin-13 group, however, pyramidal neuron and glial cell damage was less than those without apelin-13. Cisplatin increased TrkB activity in the hippocampus, which was counteracted by apelin-13. In conclusion, apelin-13 reduced the cisplatininduced cognitive deficiency, by suppressing inflammation and stimulating the synthesis and activation of neurotrophic factors in hippocampal tissue.